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1.
Int J Mol Sci ; 25(9)2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38732116

RESUMEN

Hypertension is a pervasive and widespread health condition that poses a significant risk factor for cardiovascular disease, which includes conditions such as heart attack, stroke, and heart failure. Despite its widespread occurrence, the exact cause of hypertension remains unknown, and the mechanisms underlying the progression from prehypertension to hypertension require further investigation. Recent proteomic studies have shown promising results in uncovering potential biomarkers related to disease development. In this study, serum proteomic data collected from Qatar Biobank were analyzed to identify altered protein expression between individuals with normal blood pressure, prehypertension, and hypertension and to elucidate the biological pathways contributing to this disease. The results revealed a cluster of proteins, including the SRC family, CAMK2B, CAMK2D, TEC, GSK3, VAV, and RAC, which were markedly upregulated in patients with hypertension compared to those with prehypertension (fold change ≥ 1.6 or ≤-1.6, area under the curve ≥ 0.8, and q-value < 0.05). Pathway analysis showed that the majority of these proteins play a role in actin cytoskeleton remodeling. Actin cytoskeleton reorganization affects various biological processes that contribute to the maintenance of blood pressure, including vascular tone, endothelial function, cellular signaling, inflammation, fibrosis, and mechanosensing. Therefore, the findings of this study suggest a potential novel role of actin cytoskeleton-related proteins in the progression from prehypertension to hypertension. The present study sheds light on the underlying pathological mechanisms involved in hypertension and could pave the way for new diagnostic and therapeutic approaches for the treatment of this disease.


Asunto(s)
Citoesqueleto de Actina , Hipertensión , Proteómica , Humanos , Hipertensión/metabolismo , Proteómica/métodos , Masculino , Femenino , Persona de Mediana Edad , Citoesqueleto de Actina/metabolismo , Prehipertensión/metabolismo , Biomarcadores , Proteoma/metabolismo , Adulto , Presión Sanguínea , Anciano
2.
J Appl Physiol (1985) ; 132(6): 1460-1467, 2022 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-35546127

RESUMEN

Angiotensin-converting enzyme 2 (ACE2) or exercise training (ExT) is beneficial to hypertension, but their combined effects remain unknown. In this study, lentivirus containing enhanced green fluorescent protein (eGFP) and ACE2 were microinjected into the paraventricular nucleus (PVN) of young male spontaneous hypertensive rats (SHRs), and SHRs were assigned into five groups: sedentary (SHR), SHR-ExT, SHR-eGFP, ACE2 gene (SHR-ACE2), and ACE2 gene combined with ExT (SHR-ACE2-ExT). Wistar-Kyoto (WKY) rats were used as a control. ACE2 gene or ExT significantly delayed the elevation of blood pressure, and the combined effect prevented the development and progression of prehypertension. Either ACE2 overexpression or ExT improved arterial baroreflex sensitivity (BRS), whereas the combined effect normalized BRS in SHR. Compared with SHR, SHR-ACE2 and SHR-ExT displayed a significantly higher level of ACE2 protein but had lower plasma norepinephrine (NE) and angiotensin II (AngII) as well as angiotensin II type 1 receptor (AT1) protein expression in the PVN. SHR-ACE2-ExT showed the largest decrease in AngII and AT1 protein expression. Reactive oxygen species (ROS) level and NADPH oxidase (NOX2 and NOX4) protein expression in PVN were also decreased in SHR-ACE2-ExT group than in SHR-ACE2 and SHR-ExT groups. It was concluded that the combined effect has effectively prevented prehypertension progression and baroreflex dysfunction in SHR, which is associated with the reduction in AngII/AT1 axis function and oxidative stress in the PVN.NEW & NOTEWORTHY Angiotensin-converting enzyme 2 (ACE2) gene in combination with exercise training (ExT) delayed the progression of hypertension via normalizing the blunted baroreflex sensitivity (BRS) and inhibiting sympathetic nerve activity (SNA). Its underlying mechanism may be related to the inhibition of AngII/AT1 axis function and central oxidative stress in the paraventricular nucleus (PVN) of prehypertensive rats.


Asunto(s)
Angiotensina II/metabolismo , Angiotensina I/metabolismo , Enzima Convertidora de Angiotensina 2/metabolismo , Hipertensión , Condicionamiento Físico Animal , Prehipertensión , Animales , Presión Sanguínea , Hipertensión/metabolismo , Hipertensión/terapia , Masculino , Estrés Oxidativo/fisiología , Núcleo Hipotalámico Paraventricular , Condicionamiento Físico Animal/fisiología , Prehipertensión/metabolismo , Ratas , Ratas Endogámicas SHR , Ratas Endogámicas WKY
3.
J Cardiovasc Transl Res ; 15(5): 1049-1063, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-35391709

RESUMEN

This study investigated the effects of prehypertension and shear stress on the reendothelialization potential of human early EPCs and explored its potential mechanisms. Early EPCs from the prehypertensive patients showed reduced migration and adhesion in vitro and demonstrated a significantly impaired in vivo reendothelialization capacity. Shear stress pretreatment markedly promoted the in vivo reendothelialization capacity of EPCs. Although basal CXCR4 expression in early EPCs from prehypertensive donors was similar to that from healthy control, SDF-1-induced phosphorylation of CXCR4 was lower in prehypertensive EPCs. Shear stress up-regulated CXCR4 expression and increased CXCR4 phosphorylation, and restored the SDF-1/CXCR4-dependent JAK-2 phosphorylation in prehypertensive EPCs. CXCR4 knockdown or JAK-2 inhibitor treatment prevents against shear stress-induced increase in the migration, adhesion and reendothelialization capacity of the prehypertensive EPCs. Collectively, CXCR4 receptor profoundly modulates the reendothelialization potential of early EPCs. The abnormal CXCR4-mediated JAK-2 signaling may contribute to impaired functions of EPCs from patients with prehypertension.


Asunto(s)
Células Progenitoras Endoteliales , Prehipertensión , Humanos , Células Progenitoras Endoteliales/metabolismo , Prehipertensión/metabolismo , Endotelio Vascular/metabolismo , Estrés Mecánico , Receptores CXCR4/metabolismo , Transducción de Señal , Células Cultivadas
4.
Clin Exp Hypertens ; 43(2): 112-119, 2021 Feb 17.
Artículo en Inglés | MEDLINE | ID: mdl-32896167

RESUMEN

OBJECTIVE: We studied the link of decreased baroreflex sensitivity (BRS) to cardiometabolic risks and prehypertension status in postmenopausal women during their early menopausal phase. METHODS: Premenopausal women (n = 55) and early-postmenopausal women (n = 50) of age group between 40 and 55 years were recruited for the study, and their anthropometric parameters, complete battery of autonomic function tests (AFT), BRS, hormone levels, and cardiometabolic risk parameters were measured and compared between two groups. Correlation analysis of BRS with various physiological and biochemical parameters in these two groups were performed. Multiple regression analysis of BRS with various other associated factors in postmenopausal subjects and bivariate logistic regression analysis for assessing prediction of prehypertension status by BRS in postmenopausal group were performed. RESULTS: There was a significant difference in AFT and metabolic parameters between premenopausal and postmenopausal women. Sympathovagal imbalance (increased sympathetic and decreased parasympathetic) was prominent in early-postmenopausal women. Decreased BRS, the marker of cardiovascular (CV) risk was found to be significant (P < .001) and correlated with various cardiometabolic parameters in early-postmenopausal subjects. Multiple regression analysis demonstrated that decreased BRS is independently linked to parameters of decreased vagal activity, inflammation, and oxidative stress in early-postmenopausal group. Decreased BRS could predict prehypertension status in early-postmenopausal subjects as confirmed by bivariate logistic regression analysis. CONCLUSION: Sympathovagal imbalance, decreased BRS and considerable metabolic derangements were observed in women in their early phase of menopause. Decreased BRS appears to be associated with the cardiometabolic risks in these women. Prehypertension status in early-postmenopausal subjects could be predicted by decreased BRS.


Asunto(s)
Barorreflejo/fisiología , Posmenopausia/fisiología , Prehipertensión , Biomarcadores/sangre , Presión Sanguínea/fisiología , Factores de Riesgo Cardiometabólico , Femenino , Frecuencia Cardíaca/fisiología , Humanos , Inflamación/fisiopatología , Persona de Mediana Edad , Estrés Oxidativo , Prehipertensión/diagnóstico , Prehipertensión/metabolismo , Prehipertensión/fisiopatología , Nervio Vago/fisiopatología
5.
Circ J ; 84(8): 1294-1303, 2020 07 22.
Artículo en Inglés | MEDLINE | ID: mdl-32522899

RESUMEN

BACKGROUND: The effects of hypertension and exercise training (T) on the sequential interplay between renin-angiotensin system (RAS), autonomic control and heart remodeling during the development of hypertension in spontaneously hypertensive rats (SHR), was evaluated.Methods and Results:Time course changes of these parameters were recorded in 4-week-old SHR submitted to a T or sedentary (S) protocol. Wistar Kyoto rats served as controls. Hemodynamic recordings were obtained in conscious rats at experimental weeks 0, 1, 2, 4, and 8. The left ventricle (LV) was collected to evaluate RAS gene and protein expression, cardiomyocytes' hypertrophy and collagen accumulation. Pre-hypertensive SHR exhibited augmented AT1R gene expression; at 5 weeks, they presented with elevated pressure, increased LV angiotensinogen and ACE mRNA expression, followed by sympathoexcitation (from the 8thweek onwards). Marked AT1R protein content, myocytes's hypertrophy, collagen deposition and increased pressure variability were observed in 12-week-old sedentary SHR. In addition to attenuating all these effects, T activated Mas receptor expression augmented parasympathetic modulation of the heart, and delayed the onset and reduced the magnitude, but did not block the development of genetic hypertension. CONCLUSIONS: The close temporal relationship between changes in the LV ACE-Ang II-AT1R axis, autonomic control and cardiac remodeling at both the establishment of hypertension and during exercise training reveals the essential role played by the AT1R pathway in driving cardiac remodeling and autonomic modulation during the transition from the pre- to hypertensive phase.


Asunto(s)
Terapia por Ejercicio , Corazón/inervación , Hipertensión/prevención & control , Prehipertensión/terapia , Receptor de Angiotensina Tipo 1/metabolismo , Sistema Nervioso Simpático/fisiopatología , Función Ventricular Izquierda , Remodelación Ventricular , Animales , Presión Sanguínea , Modelos Animales de Enfermedad , Regulación hacia Abajo , Hipertensión/genética , Hipertensión/metabolismo , Hipertensión/fisiopatología , Prehipertensión/genética , Prehipertensión/metabolismo , Prehipertensión/fisiopatología , Ratas Endogámicas SHR , Ratas Endogámicas WKY , Receptor de Angiotensina Tipo 1/genética , Transducción de Señal , Factores de Tiempo
6.
Am J Physiol Heart Circ Physiol ; 319(2): H271-H281, 2020 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-32559139

RESUMEN

The purpose of this study was to investigate the effect of race and subclinical elevations in blood pressure (i.e., prehypertension) on cutaneous sensory nerve-mediated and nitric oxide (NO)-dependent vasodilation. We recruited participants who self-identified as either non-Hispanic black (n = 16) or non-Hispanic white (n = 16). Within each group, participants were subdivided as either normotensive (n = 8 per group) or prehypertensive (n = 8 per group). Each participant was instrumented with four intradermal microdialysis fibers: 1) control (lactated Ringer's), 2) 5% lidocaine (sensory nerve inhibition), 3) 20 mM Nω-nitro-l-arginine methyl ester (l-NAME) (NO synthase inhibition), and 4) lidocaine + l-NAME. Skin blood flow was assessed via laser-Doppler flowmetry, and each site underwent local heating from 33°C to 39°C. At the plateau, 20 mM l-NAME were infused at control and lidocaine sites to quantify NO-dependent vasodilation. Maximal vasodilation was induced via 54 mM sodium nitroprusside and local heating to 43°C. Data are means ± SD. Sensory nerve-mediated cutaneous vasodilation was reduced in prehypertensive non-Hispanic white (34 ± 7%) and both non-Hispanic black groups (normotensive, 20 ± 9%, prehypertensive, 24 ± 15%) relative to normotensive non-Hispanic whites (54 ± 12%). NO-dependent vasodilation was also reduced in prehypertensive non-Hispanic white (41 ± 7%) and both non-Hispanic black groups (normotensive, 44 ± 7%, prehypertensive, 19 ± 7%) relative to normotensive non-Hispanic whites (60 ± 11%). The decrease in NO-dependent vasodilation in prehypertensive non-Hispanic blacks was further reduced relative to all other groups. These data suggest subclinical increases in blood pressure adversely affect sensory-mediated and NO-dependent vasodilation in both non-Hispanic blacks and whites.NEW & NOTEWORTHY Overt hypertension is known to reduce cutaneous sensory nerve-mediated and nitric oxide (NO)-dependent vasodilation, but the effect of subclinical increases in blood pressure (i.e., prehypertension) is unknown. The combined effect of race and prehypertension is also unknown. In this study, we found that prehypertension reduces cutaneous sensory nerve-mediated and NO-dependent vasodilation in both non-Hispanic white and black populations, with the greatest reductions observed in prehypertensive non-Hispanic blacks.


Asunto(s)
Presión Sanguínea , Vasos Sanguíneos/inervación , Vasos Sanguíneos/metabolismo , Células Endoteliales/metabolismo , Óxido Nítrico/metabolismo , Prehipertensión/fisiopatología , Células Receptoras Sensoriales , Piel/irrigación sanguínea , Vasodilatación , Administración Cutánea , Adolescente , Adulto , Negro o Afroamericano , Anestésicos Locales/administración & dosificación , Vasos Sanguíneos/efectos de los fármacos , Estudios de Casos y Controles , Células Endoteliales/efectos de los fármacos , Inhibidores Enzimáticos/administración & dosificación , Femenino , Georgia/epidemiología , Humanos , Masculino , Microdiálisis , Óxido Nítrico Sintasa/antagonistas & inhibidores , Óxido Nítrico Sintasa/metabolismo , Prehipertensión/diagnóstico , Prehipertensión/etnología , Prehipertensión/metabolismo , Factores Raciales , Células Receptoras Sensoriales/efectos de los fármacos , Vasodilatación/efectos de los fármacos , Vasodilatadores/administración & dosificación , Población Blanca , Adulto Joven
7.
Sci Rep ; 10(1): 9974, 2020 06 19.
Artículo en Inglés | MEDLINE | ID: mdl-32561792

RESUMEN

There are few studies assessing pre-hypertension and an impaired fasting glucose (IFG) and their combined effects on the cancer risk. We investigated the impact of pre-hypertension on cancer risk and IFG, and their combined effects on the cancer risk. This study included 371,762 subjects (≥40 years) who had never been diagnosed with hypertension, diabetes mellitus (DM), and cancer before. During a mean follow-up of 10.06 ± 1.86 years, 35,605 (9.58%) of the subjects developed cancer. In men only, cancer risk was significantly increased with an increase in the blood pressure (BP) (P for trend < 0.001), and were increased in the hypertension range, but not the pre-hypertension range. When analyzing the combination effect of BP and fasting glucose, cancer risks were serially increased with an increase in the fasting glucose in a dose-dependent manner, but not with an increase in BP. These results were more consistently significant in the never-smoker and non-alcohol drinking groups. However, in women, there was no significant difference. In conclusions, increased BP status or the fasting serum glucose level status were associated with cancer risk in men. Furthermore, the combination of both pre-hypertension and IFG also was associated with a cancer risk in men.


Asunto(s)
Neoplasias/etiología , Prehipertensión/complicaciones , Glucemia/metabolismo , Presión Sanguínea/fisiología , Índice de Masa Corporal , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/metabolismo , Ayuno/sangre , Ayuno/fisiología , Femenino , Humanos , Hipertensión/sangre , Hipertensión/metabolismo , Masculino , Persona de Mediana Edad , Neoplasias/sangre , Neoplasias/metabolismo , Estado Prediabético/sangre , Estado Prediabético/metabolismo , Prehipertensión/sangre , Prehipertensión/metabolismo , Factores de Riesgo
8.
J Clin Endocrinol Metab ; 105(9)2020 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-32506135

RESUMEN

CONTEXT: Although dietary potassium and sodium intake may influence calcium-phosphate metabolism and bone health, the effects on bone mineral parameters, including fibroblast growth factor 23 (FGF23), are unclear. OBJECTIVE: Here, we investigated the effects of potassium or sodium supplementation on bone mineral parameters. DESIGN, SETTING, PARTICIPANTS: We performed a post hoc analysis of a dietary controlled randomized, blinded, placebo-controlled crossover trial. Prehypertensive individuals not using antihypertensive medication (n = 36) received capsules containing potassium chloride (3 g/d), sodium chloride (3 g/d), or placebo. Linear mixed-effect models were used to estimate treatment effects. RESULTS: Potassium supplementation increased plasma phosphate (from 1.10 ± 0.19 to 1.15 ± 0.19 mmol/L, P = 0.004), in line with an increase in tubular maximum of phosphate reabsorption (from 0.93 ± 0.21 to 1.01 ± 0.20 mmol/L, P < 0.001). FGF23 decreased (114.3 [96.8-135.0] to 108.5 [93.5-125.9] RU/mL, P = 0.01), without change in parathyroid hormone and 25-hydroxy vitamin D3. Fractional calcium excretion decreased (from 1.25 ± 0.50 to 1.11 ± 0.46 %, P = 0.03) without change in plasma calcium. Sodium supplementation decreased both plasma phosphate (from 1.10 ± 0.19 to 1.06 ± 0.21 mmol/L, P = 0.03) and FGF23 (from 114.3 [96.8-135.0] to 108.7 [92.3-128.1] RU/mL, P = 0.02). Urinary and fractional calcium excretion increased (from 4.28 ± 1.91 to 5.45 ± 2.51 mmol/24 hours, P < 0.001, and from 1.25 ± 0.50 to 1.44 ± 0.54 %, P = 0.004, respectively). CONCLUSIONS: Potassium supplementation led to a decrease in FGF23, which was accompanied by increase in plasma phosphate and decreased calcium excretion. Sodium supplementation reduced FGF23, but this was accompanied by decrease in phosphate and increase in fractional calcium excretion. Our results indicate distinct effects of potassium and sodium intake on bone mineral parameters, including FGF23. CLINICAL TRIAL REGISTRATION NUMBER: NCT01575041.


Asunto(s)
Homeostasis/efectos de los fármacos , Minerales/metabolismo , Potasio/administración & dosificación , Prehipertensión/dietoterapia , Sodio en la Dieta/administración & dosificación , Anciano , Anciano de 80 o más Años , Huesos/efectos de los fármacos , Huesos/metabolismo , Calcio/sangre , Colecalciferol/sangre , Estudios Cruzados , Suplementos Dietéticos , Método Doble Ciego , Femenino , Factor-23 de Crecimiento de Fibroblastos , Humanos , Masculino , Persona de Mediana Edad , Hormona Paratiroidea/sangre , Fosfatos/sangre , Prehipertensión/metabolismo , Estudios Retrospectivos
9.
J Clin Hypertens (Greenwich) ; 22(6): 1025-1032, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-32442359

RESUMEN

For normal-weight population, the management of prehypertension may be more beneficial by identifying insulin resistance (IR) status than relying solely on traditional indicators of obesity. We investigated the association of triglyceride glucose (TyG) index, a simple surrogate marker of IR, and its combination of obesity indices with prehypertension in lean individuals. A total of 105 070 lean adults without hypertension were included in this analysis. Body mass index (BMI), waist circumference (WC), waist-to-height ratio (WtHR), and TyG were calculated according to the corresponding formula; TyG-BMI, TyG-WC, and TyG-WHtR were calculated by multiplying the corresponding two parameters. Gardner-Altman plots, partial correlation, and logistic regression analyses were applied to explore the associations in continuous variables and quartiles. The prehypertensive ones had higher mean values of TyG, TyG-BMI, TyG-WC, and TyG-WHtR than normotensive individuals. All the four indicators showed positive correlations with systolic blood pressure and diastolic blood pressure. After full adjustment, only TyG-BMI and TyG-WC were significantly associated with prehypertension in both genders. Furthermore, TyG-BMI had the highest OR for prehypertension. Our study showed that TyG-BMI might be an accessible and complementary monitor in the hierarchical management of non-obese prehypertensive patients.


Asunto(s)
Glucosa , Hipertensión , Prehipertensión , Triglicéridos , Adulto , Glucemia/metabolismo , Índice de Masa Corporal , China/epidemiología , Estudios Transversales , Femenino , Glucosa/metabolismo , Humanos , Hipertensión/diagnóstico , Hipertensión/epidemiología , Hipertensión/metabolismo , Masculino , Obesidad/diagnóstico , Obesidad/epidemiología , Obesidad/metabolismo , Prehipertensión/diagnóstico , Prehipertensión/epidemiología , Prehipertensión/metabolismo , Factores de Riesgo , Triglicéridos/metabolismo
10.
Am J Physiol Renal Physiol ; 318(6): F1409-F1417, 2020 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-32390511

RESUMEN

Glucagon-like peptide-1 (GLP-1) is an incretin hormone known to stimulate postprandial insulin release. However, GLP-1 also exerts extrapancreatic effects, including renal effects. Some of these renal effects are attenuated in hypertensive rats, where renal expression of GLP-1 receptors is reduced. Here, we assessed the expression and vascular function of GLP-1 receptors in kidneys from young prehypertensive rats. We also examined GLP-1-induced vasodilation in the renal vasculature in wild-type (WT) and GLP-1 receptor knockout mice using wire and pressure myography and the isolated perfused juxtamedullary nephron preparation. We investigated whether GLP-1 and the metabolite GLP-1(9-36)amide had renal vascular effects independent of the known GLP-1 receptor. We hypothesized that hypertension decreased expression of renal GLP-1 receptors. We also hypothesized that GLP-1-induced renal vasodilatation depended on expression of the known GLP-1 receptor. In contrast to normotensive rats, no immunohistochemical staining or vasodilatory function of GLP-1 receptors was found in kidneys from prehypertensive rats. In WT mice, GLP-1 induced renal vasodilation and reduced the renal autoregulatory response. The GLP-1 receptor antagonist exendin 9-39 inhibited relaxation, and GLP-1(9-36)amide had no vasodilatory effect. In GLP-1 receptor knockout mice, no relaxation induced by GLP-1 or GLP-1(9-36)amide was found, the autoregulatory response in afferent arterioles was normal, and no GLP-1-induced reduction of autoregulation was found. We conclude that in prehypertensive kidneys, expression and function of GLP-1 receptors is lost. The renal vasodilatory effect of GLP-1 is mediated exclusively by the known GLP-1 receptor. GLP-1(9-36)amide has no renal vasodilatory effect. GLP-1 attenuates renal autoregulation by reducing the myogenic response.


Asunto(s)
Arteriolas/efectos de los fármacos , Presión Sanguínea/efectos de los fármacos , Péptido 1 Similar al Glucagón/farmacología , Receptor del Péptido 1 Similar al Glucagón/agonistas , Riñón/irrigación sanguínea , Prehipertensión/metabolismo , Arteria Renal/efectos de los fármacos , Vasodilatación/efectos de los fármacos , Vasodilatadores/farmacología , Animales , Arteriolas/metabolismo , Arteriolas/fisiopatología , Modelos Animales de Enfermedad , Femenino , Péptido 1 Similar al Glucagón/análogos & derivados , Receptor del Péptido 1 Similar al Glucagón/genética , Receptor del Péptido 1 Similar al Glucagón/metabolismo , Masculino , Ratones Endogámicos C57BL , Ratones Noqueados , Prehipertensión/genética , Prehipertensión/fisiopatología , Ratas Endogámicas SHR , Arteria Renal/metabolismo , Arteria Renal/fisiopatología
11.
Metab Syndr Relat Disord ; 17(7): 374-379, 2019 09.
Artículo en Inglés | MEDLINE | ID: mdl-31211636

RESUMEN

Background: Insulin resistance (IR) is the common pathophysiology of prehypertension and prediabetes. Recognition of IR in one of the two disease states is critical for carrying out preventive strategies of another disease state. This study aimed to explore which simple IR indexes were significantly associated with prehypertension in subjects with normoglycemia. Methods: A total of 108,370 adults without elevated fasting plasma glucose and hypertension were included in this study. The three simple IR indexes [triglycerides to high-density lipoprotein cholesterol ratio, the product of fasting triglycerides and glucose, and metabolic score for IR (METS-IR)] were calculated. Partial correlation was used to analyze the correlation between the three indicators and blood pressure (BP) levels, and logistic regression analysis was used to explore their association with prehypertension. Results: Among the three indicators, only METS-IR had positive correlations with systolic and diastolic blood pressure levels. Furthermore, METS-IR was also significantly associated with prehypertension, irrespective of the categorization of waist circumference (WC). The odds ratios of the highest quartile were 2.223 (95% confidence interval [CI]: 2.044-2.417) in all subjects, 2.022 (95% CI: 1.501-2.725) in elevated WC subgroup, and 1.815 (95% CI: 1.620-2.034) in normal WC subgroup. Conclusions: METS-IR was associated with prehypertension in normoglycemic Chinese subjects, which bypasses the impact of WC and might be valuable for the management of prehypertension and the prevention of prediabetes in different ethnic groups.


Asunto(s)
Glucemia/metabolismo , Indicadores de Salud , Resistencia a la Insulina , Prehipertensión/epidemiología , Adulto , Índice de Masa Corporal , HDL-Colesterol/sangre , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prehipertensión/complicaciones , Prehipertensión/metabolismo , Factores de Riesgo , Triglicéridos/sangre , Circunferencia de la Cintura
12.
J Am Heart Assoc ; 8(9): e012016, 2019 05 07.
Artículo en Inglés | MEDLINE | ID: mdl-31039659

RESUMEN

Background Previous studies demonstrated that angiotensin (Ang) III , not Ang II , is the predominant endogenous agonist for Ang type-2 receptor ( AT 2R)-induced natriuresis in normal rats, and that hypertensive 12-week-old spontaneously hypertensive rats ( SHR ) lack natriuretic responses to Ang III . This study tested whether prehypertensive SHR already have defective Ang III -induced natriuresis and determined possible mechanisms. Methods and Results Female and male normotensive 4-week-old SHR and Wistar Kyoto rats were studied after 24-hour systemic AT 1R blockade. Left kidneys received 30 minute renal interstitial infusions of vehicle followed by Ang III (3.5, 7.0, 14, and 28 nmol/kg per min; each dose for 30 minutes). Right kidneys received vehicle infusions. In 4-week-old Wistar Kyoto rats, renal interstitial Ang III increased urine sodium (Na+) excretion but failed to induce natriuresis in 4-week-old SHR . Renal Ang III levels were similar between Wistar Kyoto rats and SHR , making increased Ang III degradation as a possible cause for defective natriuresis in SHR unlikely. In Wistar Kyoto rats, renal interstitial Ang III induced translocation of AT 2Rs to apical plasma membranes of renal proximal tubule cells. Simultaneously, Ang III induced retraction of the major Na+ transporter Na+-H+ exchanger-3 ( NHE -3) from apical membranes and internalization of Na+/K+ ATP ase ( NKA ) from basolateral membranes of renal proximal tubule cells. Consistent with NHE -3 and NKA retraction, Ang III increased pS er552- NHE -3 and decreased pS er23- NKA . In contrast, in SHR , intrarenal Ang III failed to induce AT 2R translocation, NHE -3 or NKA retraction, pS er552- NHE -3 phosphorylation, or pS er23- NKA dephosphorylation. Conclusions These results indicate impaired Ang III / AT 2R signaling as a possible primary defect in prehypertensive SHR .


Asunto(s)
Angiotensina III/administración & dosificación , Presión Arterial/efectos de los fármacos , Riñón/efectos de los fármacos , Natriuresis/efectos de los fármacos , Prehipertensión/metabolismo , Receptor de Angiotensina Tipo 2/agonistas , Sistema Renina-Angiotensina/efectos de los fármacos , Animales , Modelos Animales de Enfermedad , Femenino , Riñón/metabolismo , Riñón/fisiopatología , Masculino , Fosforilación , Prehipertensión/fisiopatología , Ratas Endogámicas SHR , Ratas Endogámicas WKY , Receptor de Angiotensina Tipo 2/metabolismo , Transducción de Señal , Intercambiador 3 de Sodio-Hidrógeno/metabolismo , ATPasa Intercambiadora de Sodio-Potasio/metabolismo
13.
Chin J Integr Med ; 24(12): 897-904, 2018 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-30341486

RESUMEN

OBJECTIVE: To evaluate whether the berberine treatment can improve endothelial repair capacity of early endothelial progenitor cells (EPCs) from prehypertensive subjects through increasing CXC chemokine receptor 4 (CXCR4) signaling. METHODS: EPCs were isolated from prehypertensive and healthy subjects and cultured. In vivo reendothelialization capacity of EPCs from prehypertensive patients with or without in vitro berberine treatment was examined in a nude mouse model of carotid artery injury. The protein expressions of CXCR4/Janus kinase-2 (JAK-2) signaling of in vitro EPCs were detected by Western blot analysis. RESULTS: CXCR4 signaling and alteration in migration and adhesion functions of EPCs were evaluated. Basal CXCR4 expression was significantly reduced in EPCs from prehypertensive patients compared with normal subjects (P<0.01). Also, the phosphorylation of JAK-2 of EPCs, a CXCR4 downstream signaling, was significantly decreased (P<0.01). Berberine promoted CXCR4/JAK-2 signaling expression of in vitro EPCs (P<0.01). Transplantation of EPCs pretreated with berberine markedly accelerated in vivo reendothelialization (P<0.01). The increased in vitro function and in vivo reendothelialization capacity of EPCs were inhibited by CXCR4 neutralizing antibody or pretreatment with JAK-2 inhibitor AG490, respectively (P<0.01). CONCLUSION: Berberinemodified EPCs via up-regulation of CXCR4 signaling contributes to enhanced endothelial repair capacity in prehypertension, indicating that berberine may be used as a novel potential primary prevention means against prehypertension-related atherosclerotic cardiovascular disease.


Asunto(s)
Berberina/farmacología , Células Progenitoras Endoteliales/metabolismo , Prehipertensión/metabolismo , Prehipertensión/patología , Receptores CXCR4/metabolismo , Células Progenitoras Endoteliales/efectos de los fármacos , Células Progenitoras Endoteliales/patología , Células Progenitoras Endoteliales/trasplante , Humanos , Janus Quinasa 2/metabolismo , Masculino , Transducción de Señal/efectos de los fármacos
14.
Sci Rep ; 8(1): 7749, 2018 05 17.
Artículo en Inglés | MEDLINE | ID: mdl-29773847

RESUMEN

High uric acid (UA) level and high salt intake are reportedly associated with cardiovascular disease. This study investigated the association between UA and urinary sodium excretion, as well as its interaction on the risk of prehypertension. A total of 1869 participants without hypertension were recruited from a previously established cohort in Shaanxi Province, China. The participants were classified as normotensive or prehypertensive on the basis of their blood pressure. Increasing quartiles of sodium excretion were associated with high urinary UA/creatinine levels in prehypertensive participants. Estimated sodium excretion positively correlated with urinary UA/creatinine excretions in the prehypertensive group. In addition, the multivariate-adjusted odds ratios for prehypertension compared with normotension were 1.68 (1.27-2.22) for sodium excretion and 1.71 (1.21-2.42) for serum UA. Increasing sodium excretion and serum UA were associated with higher risk of prehypertension. Compared with the lowest quartiles, the highest sodium excretion and serum UA quartiles entailed 3.48 times greater risk of prehypertension. Sodium excretion is associated with urinary UA excretion in prehypertensive participants. The present study shows that high levels of salt intake and serum UA simultaneously are associated with a higher risk of prehypertension.


Asunto(s)
Prehipertensión/diagnóstico , Prehipertensión/epidemiología , Sodio/metabolismo , Ácido Úrico/metabolismo , Adulto , Presión Sanguínea , China/epidemiología , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prehipertensión/etiología , Prehipertensión/metabolismo , Pronóstico , Factores de Riesgo , Adulto Joven
15.
Am J Hypertens ; 31(9): 1013-1023, 2018 08 03.
Artículo en Inglés | MEDLINE | ID: mdl-29767672

RESUMEN

BACKGROUND: Toll-like receptor 4 (TLR4) has been implicated in the progression of cardiovascular disease, including hypertension. However, the role of TLR4 in the development of prehypertension is uncertain. METHODS: Prehypertensive rats were treated with 8% salt for 12 weeks to induce prehypertension. These rats were then given either TAK-242 selective TLR4 blocker, or vehicle by bilateral micro-injection to the paraventricular nucleus (PVN). Blood pressure (BP) and renal sympathetic nerve activity were recorded. PVN expression of TLR4, myeloid differentiation factor 88 (Myd88), nuclear factor-kappa B (NF-κB) p65, proinflammation cytokines (PICs), interleukin (IL)-1ß, IL-6, tumor necrosis factor-alpha (TNF-α), nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2 (NOX2), NADPH oxidase 4 (NOX4), Cu/Zn superoxide dismutase (SOD) level, tyrosine hydroxylase, and 67 kDa isoform of glutamate decarboxylase (GAD67) were tested to determine the influence of TLR4 blockade. RESULTS: TLR4 expression increased significantly in the PVN of high-salt groups with a corresponding increase in reactive oxygen species (ROS) and PICs. TLR4 blockade significantly reduced the signaling molecules downstream TLR4 and the expression of TNF-α, IL-6, IL-1ß, decreased ROS, NOX2, NOX4 level, increased Cu/Zn-SOD, re-balanced neurotransmitters, and regulated sympathetic nerve activity in the PVN of prehypertensive rats. CONCLUSIONS: Salt-induced prehypertension is partly due to the upregulation of TLR4 in PVN. Blockade of TLR4 in the brain reduced salt-induced prehypertension response, possibly through downregulation of ROS and PICs expression, and the restorage of neurotransmitter balance in the PVN.


Asunto(s)
Antihipertensivos/farmacología , Presión Arterial/efectos de los fármacos , Citocinas/metabolismo , Mediadores de Inflamación/metabolismo , Núcleo Hipotalámico Paraventricular/efectos de los fármacos , Prehipertensión/tratamiento farmacológico , Especies Reactivas de Oxígeno/metabolismo , Sulfonamidas/farmacología , Receptor Toll-Like 4/antagonistas & inhibidores , Animales , Modelos Animales de Enfermedad , Riñón/inervación , Masculino , Núcleo Hipotalámico Paraventricular/metabolismo , Núcleo Hipotalámico Paraventricular/fisiopatología , Prehipertensión/metabolismo , Prehipertensión/fisiopatología , Ratas Sprague-Dawley , Cloruro de Sodio Dietético , Sistema Nervioso Simpático/efectos de los fármacos , Sistema Nervioso Simpático/metabolismo , Sistema Nervioso Simpático/fisiopatología , Receptor Toll-Like 4/metabolismo
16.
Hypertension ; 71(6): 1226-1238, 2018 06.
Artículo en Inglés | MEDLINE | ID: mdl-29686017

RESUMEN

Single or combinatorial administration of ß-blockers is a mainstay treatment strategy for conditions caused by sympathetic overactivity. Conventional wisdom suggests that the main beneficial effect of ß-blockers includes resensitization and restoration of ß1-adrenergic signaling pathways in the myocardium, improvements in cardiomyocyte contractility, and reversal of ventricular sensitization. However, emerging evidence indicates that another beneficial effect of ß-blockers in disease may reside in sympathetic neurons. We investigated whether ß-adrenoceptors are present on postganglionic sympathetic neurons and facilitate neurotransmission in a feed-forward manner. Using a combination of immunocytochemistry, RNA sequencing, Förster resonance energy transfer, and intracellular Ca2+ imaging, we demonstrate the presence of ß-adrenoceptors on presynaptic sympathetic neurons in both human and rat stellate ganglia. In diseased neurons from the prehypertensive rat, there was enhanced ß-adrenoceptor-mediated signaling predominantly via ß2-adrenoceptor activation. Moreover, in human and rat neurons, we identified the presence of the epinephrine-synthesizing enzyme PNMT (phenylethanolamine-N-methyltransferase). Using high-pressure liquid chromatography with electrochemical detection, we measured greater epinephrine content and evoked release from the prehypertensive rat cardiac-stellate ganglia. We conclude that neurotransmitter switching resulting in enhanced epinephrine release, may provide presynaptic positive feedback on ß-adrenoceptors to promote further release, that leads to greater postsynaptic excitability in disease, before increases in arterial blood pressure. Targeting neuronal ß-adrenoceptor downstream signaling could provide therapeutic opportunity to minimize end-organ damage caused by sympathetic overactivity.


Asunto(s)
Neurotransmisores/metabolismo , Prehipertensión/metabolismo , Receptores Adrenérgicos beta/metabolismo , Ganglio Estrellado/metabolismo , Sistema Nervioso Simpático/fisiopatología , Agonistas alfa-Adrenérgicos/farmacología , Animales , Modelos Animales de Enfermedad , Ensayo de Inmunoadsorción Enzimática , Humanos , Inmunohistoquímica , Masculino , Prehipertensión/fisiopatología , Ratas Endogámicas SHR , Transducción de Señal , Ganglio Estrellado/efectos de los fármacos , Sistema Nervioso Simpático/efectos de los fármacos , Transmisión Sináptica
17.
J Clin Hypertens (Greenwich) ; 20(2): 273-279, 2018 02.
Artículo en Inglés | MEDLINE | ID: mdl-29316211

RESUMEN

We aimed to elucidate the role of autonomic dysfunction in the context of complex metabolic and cardiovascular changes in subjects with prehypertension. We identified 556 asymptomatic subjects without hypertension who underwent comprehensive cardiovascular exams. We obtained heart rate recovery (HRR) after peak exercise to quantitatively measure autonomic dysfunction. Of the 556 participants, 279 individuals had prehypertension and the remaining 277 had optimal BP. HRR was significantly lower in the prehypertension group (36.0 ± 14.5 bpm) than in the optimal BP group (39.3 ± 14.7 bpm, P = .009). The prehypertension group more frequently demonstrated features of metabolic disturbances and subclinical target organ damage. Among the various baseline cardiovascular and metabolic factors assessed, resting systolic BP and high-density lipoprotein cholesterol level were independent determinants of HRR (both P < .05). Autonomic dysfunction coexists with prehypertension and is closely linked to changes in systolic BP and lipid metabolism.


Asunto(s)
Enfermedades del Sistema Nervioso Autónomo , HDL-Colesterol/sangre , Enfermedades Metabólicas , Prehipertensión , Enfermedades del Sistema Nervioso Autónomo/complicaciones , Enfermedades del Sistema Nervioso Autónomo/diagnóstico , Enfermedades del Sistema Nervioso Autónomo/fisiopatología , Presión Sanguínea/fisiología , Sistema Cardiovascular/fisiopatología , Correlación de Datos , Estudios Transversales , Prueba de Esfuerzo/métodos , Femenino , Frecuencia Cardíaca/fisiología , Humanos , Masculino , Enfermedades Metabólicas/complicaciones , Enfermedades Metabólicas/diagnóstico , Enfermedades Metabólicas/fisiopatología , Persona de Mediana Edad , Prehipertensión/complicaciones , Prehipertensión/diagnóstico , Prehipertensión/metabolismo , Prehipertensión/fisiopatología , República de Corea/epidemiología
18.
J Am Soc Hypertens ; 12(1): 42-49, 2018 01.
Artículo en Inglés | MEDLINE | ID: mdl-29275920

RESUMEN

Intermittent fasting is a phenomenon which can be observed in most humans. The effect of intermittent fasting on blood pressure variability (BPV) has not previously been investigated. The purpose of this study was to assess the effect of fasting on blood pressure (BP) (with office, home, central, and ambulatory blood pressure monitoring [ABPM]) and on BPV. Sixty individuals were included in the study. Office, home, ABPM, and central BP measurements were performed before and during intermittent fasting. Standard deviation and coefficient variation were used for office and home BPV measurement, while the smoothness index was used to calculate ABPM variability. Patients' BP and BPV values before and during intermittent fasting were then compared. Intermittent fasting resulted in a significant decrease in office BP values and ABPM measurements but caused no significant change in home and central BP measurements. Twenty-four hour urinary sodium excretion decreased. Smoothness values obtained from ABPM measurements were low; in other words, BPV was greater. BPV was higher in patients who woke up to eat before sunrise, but BPV was low in patients with high body mass index. Intermittent fasting produced a significant decrease in BP values in terms of office and ABPM measurements in this study but caused no significant change in central BP and home measurements. We also identified an increase in BPV during intermittent fasting, particularly in patients who rose before sunrise.


Asunto(s)
Determinación de la Presión Sanguínea , Ayuno , Hipertensión , Prehipertensión , Sodio/orina , Presión Sanguínea/fisiología , Determinación de la Presión Sanguínea/clasificación , Determinación de la Presión Sanguínea/métodos , Determinación de la Presión Sanguínea/estadística & datos numéricos , Correlación de Datos , Ayuno/fisiología , Ayuno/orina , Femenino , Humanos , Hipertensión/diagnóstico , Hipertensión/metabolismo , Hipertensión/fisiopatología , Masculino , Persona de Mediana Edad , Natriuresis/fisiología , Prehipertensión/diagnóstico , Prehipertensión/metabolismo , Prehipertensión/fisiopatología
19.
Arch Physiol Biochem ; 124(4): 357-360, 2018 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-29183155

RESUMEN

OBJECTIVE: To examine some anthropometric parameters, arterial stiffness, lipid profile, and soluble adhesion molecules in young adults with reduced physical activity. MATERIAL AND METHODS: The study is carried on 54 healthy young adults aged 20.97 ± 2.04 years. Two groups: 23 with reduced physical activity (INAC) and 31 with optimal physical activity (AC). Body mass index (BMI), basal metabolic rate (BMR), central aortic systolic blood pressure (CSBP, mmHg), plasma atherogenic index (AIP), and serum soluble cell adhesion molecules (sICAM-1, sVCAM-1) are followed up. RESULTS: CSBP [115.56 ± 10.22 vs. 105.13 ± 9.88*], AIP [-0.04 ± 0.18 vs. -0.08 ± 0.08**] and sICAM-1 [362.5 ± 49.95 vs. 281.75 ± 80.39**] are significantly higher, and BMR [1431 ± 297.9 vs. 1674.6 ± 365.57*] is significantly lower in the physically inactive young healthy adults. CONCLUSIONS: CSBP, AIP, and sICAM-1 are higher in young adults with reduced physical activity. This plays substantial role in the acceleration of atherogenic process and in long-term perspective could promote cardiovascular diseases.


Asunto(s)
Enfermedades Asintomáticas , Aterosclerosis/fisiopatología , Molécula 1 de Adhesión Intercelular/sangre , Prehipertensión/fisiopatología , Conducta Sedentaria , Regulación hacia Arriba , Rigidez Vascular , Adolescente , Adulto , Enfermedades Asintomáticas/epidemiología , Enfermedades Asintomáticas/terapia , Aterosclerosis/epidemiología , Aterosclerosis/metabolismo , Aterosclerosis/prevención & control , Metabolismo Basal , Biomarcadores/sangre , Bulgaria/epidemiología , Ejercicio Físico , Estudios de Seguimiento , Humanos , Molécula 1 de Adhesión Intercelular/química , Prehipertensión/epidemiología , Prehipertensión/metabolismo , Prehipertensión/prevención & control , Factores de Riesgo , Índice de Severidad de la Enfermedad , Solubilidad , Estudiantes de Odontología , Estudiantes de Medicina , Molécula 1 de Adhesión Celular Vascular/sangre , Molécula 1 de Adhesión Celular Vascular/química , Adulto Joven
20.
Clin Exp Hypertens ; 40(1): 58-64, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29072501

RESUMEN

ABSTACT Hydrogen sulfide (H2S), nitric oxide (NO), and renin-angiotensin system (RAS) are involved in hypertension. We examined whether early treatment with sodium hydrosulfide (NaHS), an exogenous H2S donor, can regulate H2S-generating pathway, NO pathway, and the RAS, to prevent the transition from prehypertension to hypertension in spontaneously hypertensive rats (SHRs). Four-week-old SHRs and control normotensive Wistar-Kyoto (WKY) rats were assigned into three groups: WKY, SHRs, and SHR + NaHS; SHRs were injected intraperitoneally with sodium hydrosulfide (14 µmol/kg/day) for 4 weeks. SHRs exhibited hypertension at 12 weeks of age, which was blocked by early sodium hydrosulfide administration. Concentrations of H2S were increased in the kidney in SHR + NaHS group versus WKY. Sodium hydrosulfide reduces mRNA expression of four H2S-generating enzymes and decreased 3-mercaptopyruvate sulphurtransferase protein level in SHRs. Early administration of sodium hydrosulfide decreases plasma NG monomethyl-l-arginine (l-NMMA, an inhibitor of NO synthase) level and increases plasma NO level in SHRs. Next, sodium hydrosulfide administration reduces renal mRNA expression of Ren, Atp6ap2, Agt, Ace, and Agtr1a in SHRs. We conclude that early short-term sodium hydrosulfide treatment increases renal H2S concentrations, restores NO bioavailability, and blocks the RAS in the kidney, in favor of vasodilatation to prevent the development of hypertension in adult SHRs.


Asunto(s)
Expresión Génica/efectos de los fármacos , Hipertensión/prevención & control , Prehipertensión/tratamiento farmacológico , Prehipertensión/metabolismo , Sulfuros/uso terapéutico , Angiotensinógeno/genética , Animales , Presión Sanguínea , Sulfuro de Hidrógeno/metabolismo , Riñón/metabolismo , Masculino , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa/metabolismo , Peptidil-Dipeptidasa A/genética , Prehipertensión/fisiopatología , ATPasas de Translocación de Protón/genética , ARN Mensajero/metabolismo , Ratas , Ratas Endogámicas SHR , Ratas Endogámicas WKY , Receptor de Angiotensina Tipo 1/genética , Receptores de Superficie Celular/genética , Renina/genética , Sistema Renina-Angiotensina/efectos de los fármacos , Sulfuros/administración & dosificación , Sulfurtransferasas/metabolismo , Factores de Tiempo , ATPasas de Translocación de Protón Vacuolares , omega-N-Metilarginina/sangre
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