RESUMO
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.
Assuntos
Citoesqueleto de Actina , Hipertensão , Proteômica , Feminino , Humanos , Masculino , Citoesqueleto de Actina/metabolismo , Biomarcadores , Pressão Sanguínea , Hipertensão/metabolismo , Pré-Hipertensão/metabolismo , Proteoma/metabolismo , Proteômica/métodos , Quinase 3 da Glicogênio Sintase/genética , Quinase 3 da Glicogênio Sintase/metabolismo , Proteínas Proto-Oncogênicas c-vav/genética , Proteínas Proto-Oncogênicas c-vav/metabolismo , Proteínas rac de Ligação ao GTP/genética , Proteínas rac de Ligação ao GTP/metabolismoRESUMO
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.
Assuntos
Barorreflexo/fisiologia , Pós-Menopausa/fisiologia , Pré-Hipertensão , Biomarcadores/sangue , Pressão Sanguínea/fisiologia , Fatores de Risco Cardiometabólico , Feminino , Frequência Cardíaca/fisiologia , Humanos , Inflamação/fisiopatologia , Pessoa de Meia-Idade , Estresse Oxidativo , Pré-Hipertensão/diagnóstico , Pré-Hipertensão/metabolismo , Pré-Hipertensão/fisiopatologia , Nervo Vago/fisiopatologiaRESUMO
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.
Assuntos
Arteríolas/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Peptídeo 1 Semelhante ao Glucagon/farmacologia , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Rim/irrigação sanguínea , Pré-Hipertensão/metabolismo , Artéria Renal/efeitos dos fármacos , Vasodilatação/efeitos dos fármacos , Vasodilatadores/farmacologia , Animais , Arteríolas/metabolismo , Arteríolas/fisiopatologia , Modelos Animais de Doenças , Feminino , Peptídeo 1 Semelhante ao Glucagon/análogos & derivados , Receptor do Peptídeo Semelhante ao Glucagon 1/genética , Receptor do Peptídeo Semelhante ao Glucagon 1/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pré-Hipertensão/genética , Pré-Hipertensão/fisiopatologia , Ratos Endogâmicos SHR , Artéria Renal/metabolismo , Artéria Renal/fisiopatologiaRESUMO
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.
Assuntos
Pressão Sanguínea , Vasos Sanguíneos/inervação , Vasos Sanguíneos/metabolismo , Células Endoteliais/metabolismo , Óxido Nítrico/metabolismo , Pré-Hipertensão/fisiopatologia , Células Receptoras Sensoriais , Pele/irrigação sanguínea , Vasodilatação , Administração Cutânea , Adolescente , Adulto , Negro ou Afro-Americano , Anestésicos Locais/administração & dosagem , Vasos Sanguíneos/efeitos dos fármacos , Estudos de Casos e Controles , Células Endoteliais/efeitos dos fármacos , Inibidores Enzimáticos/administração & dosagem , Feminino , Georgia/epidemiologia , Humanos , Masculino , Microdiálise , Óxido Nítrico Sintase/antagonistas & inibidores , Óxido Nítrico Sintase/metabolismo , Pré-Hipertensão/diagnóstico , Pré-Hipertensão/etnologia , Pré-Hipertensão/metabolismo , Fatores Raciais , Células Receptoras Sensoriais/efeitos dos fármacos , Vasodilatação/efeitos dos fármacos , Vasodilatadores/administração & dosagem , População Branca , Adulto JovemRESUMO
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.MethodsâandâResults: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.
Assuntos
Terapia por Exercício , Coração/inervação , Hipertensão/prevenção & controle , Pré-Hipertensão/terapia , Receptor Tipo 1 de Angiotensina/metabolismo , Sistema Nervoso Simpático/fisiopatologia , Função Ventricular Esquerda , Remodelação Ventricular , Animais , Pressão Sanguínea , Modelos Animais de Doenças , Regulação para Baixo , Hipertensão/genética , Hipertensão/metabolismo , Hipertensão/fisiopatologia , Pré-Hipertensão/genética , Pré-Hipertensão/metabolismo , Pré-Hipertensão/fisiopatologia , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Receptor Tipo 1 de Angiotensina/genética , Transdução de Sinais , Fatores de TempoRESUMO
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.
Assuntos
Expressão Gênica/efeitos dos fármacos , Hipertensão/prevenção & controle , Pré-Hipertensão/tratamento farmacológico , Pré-Hipertensão/metabolismo , Sulfetos/uso terapêutico , Angiotensinogênio/genética , Animais , Pressão Sanguínea , Sulfeto de Hidrogênio/metabolismo , Rim/metabolismo , Masculino , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase/metabolismo , Peptidil Dipeptidase A/genética , Pré-Hipertensão/fisiopatologia , ATPases Translocadoras de Prótons/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Receptor Tipo 1 de Angiotensina/genética , Receptores de Superfície Celular/genética , Renina/genética , Sistema Renina-Angiotensina/efeitos dos fármacos , Sulfetos/administração & dosagem , Sulfurtransferases/metabolismo , Fatores de Tempo , ATPases Vacuolares Próton-Translocadoras , ômega-N-Metilarginina/sangueRESUMO
Uric acid is the end product of purine metabolism. Metabolic disorders of uric acid are associated with many disease states. Substantial evidence suggests the possible role of uric acid as a mediator of high blood pressure. Elevated uric acid is closely associated with new onset essential hypertension in adolescents and prehypertension; and urate-lowering agents can significantly improve these early stages of hypertension. Uric acid also influences salt sensitivity of blood pressure through two phases. Local renin-angiotensin-aldosterone system activation initiates renal damage, arteriolopathy, and endothelium dysfunction, which is followed by the dysregulation of sodium homeostasis, thereby leading to increased salt sensitivity. In this review we summarize the available evidence to contribute to a better understanding of the casual relationship between uric acid and early or intermediate stages of hypertension. We hope our review can contribute to the prevention of hypertension or provide new insights into a treatment that would slow the progression of hypertension.
Assuntos
Hipertensão/metabolismo , Pré-Hipertensão/metabolismo , Ácido Úrico/metabolismo , Adolescente , Fatores Etários , Pressão Sanguínea/fisiologia , Hipertensão Essencial , Humanos , Hipertensão/sangue , Hiperuricemia/sangue , Hiperuricemia/metabolismo , Pré-Hipertensão/sangue , Cloreto de Sódio/metabolismo , Cloreto de Sódio na Dieta/metabolismo , Ácido Úrico/sangueRESUMO
The concept of enhancing structural integrity of mitochondria has emerged as a novel therapeutic option for cardiovascular disease. Flow-induced increase in laminar shear stress is a potent physiological stimulant associated with exercise, which exerts atheroprotective effects in the vasculature. However, the effect of laminar shear stress on mitochondrial remodeling within the vascular endothelium and its related functional consequences remain largely unknown. Using in vitro and in vivo complementary studies, here, we report that aerobic exercise alleviates the release of endothelial microparticles in prehypertensive individuals and that these salutary effects are, in part, mediated by shear stress-induced mitochondrial biogenesis. Circulating levels of total (CD31(+)/CD42a(-)) and activated (CD62E(+)) microparticles released by endothelial cells were significantly decreased (â¼40% for both) after a 6-mo supervised aerobic exercise training program in individuals with prehypertension. In cultured human endothelial cells, laminar shear stress reduced the release of endothelial microparticles, which was accompanied by an increase in mitochondrial biogenesis through a sirtuin 1 (SIRT1)-dependent mechanism. Resveratrol, a SIRT1 activator, treatment showed similar effects. SIRT1 knockdown using small-interfering RNA completely abolished the protective effect of shear stress. Disruption of mitochondrial integrity by either antimycin A or peroxisome proliferator-activated receptor-γ coactivator-1α small-interfering RNA significantly increased the number of total, and activated, released endothelial microparticles, and shear stress restored these back to basal levels. Collectively, these data demonstrate a critical role of endothelial mitochondrial integrity in preserving endothelial homeostasis. Moreover, prolonged laminar shear stress, which is systemically elevated during aerobic exercise in the vessel wall, mitigates endothelial dysfunction by promoting mitochondrial biogenesis.
Assuntos
Micropartículas Derivadas de Células/metabolismo , Exercício Físico , Células Endoteliais da Veia Umbilical Humana/metabolismo , Renovação Mitocondrial , Pré-Hipertensão/metabolismo , Selectina E/genética , Selectina E/metabolismo , Feminino , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Mitocôndrias/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo , Molécula-1 de Adesão Celular Endotelial a Plaquetas/genética , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , Complexo Glicoproteico GPIb-IX de Plaquetas/genética , Complexo Glicoproteico GPIb-IX de Plaquetas/metabolismo , Pré-Hipertensão/sangue , Fluxo Sanguíneo Regional , Resveratrol , Sirtuína 1/genética , Sirtuína 1/metabolismo , Estilbenos/farmacologia , Estresse Mecânico , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismoRESUMO
BACKGROUND: Maternal protein restriction in rats increases the risk of adult offspring arterial hypertension through unknown mechanisms. OBJECTIVES: The aims of the study were to evaluate the effects of a low-protein (LP) diet during pregnancy and lactation on baseline sympathetic and respiratory activities and peripheral chemoreflex sensitivity in the rat offspring. METHODS: Wistar rat dams were fed a control [normal-protein (NP); 17% protein] or an LP (8% protein) diet during pregnancy and lactation, and their male offspring were studied at 30 d of age. Direct measurements of baseline arterial blood pressure (ABP), heart rate (HR), and respiratory frequency (Rf) as well as peripheral chemoreflex activation (potassium cyanide: 0.04%) were recorded in pups while they were awake. In addition, recordings of the phrenic nerve (PN) and thoracic sympathetic nerve (tSN) activities were obtained from the in situ preparations. Hypoxia-inducible factor 1α (HIF-1α) expression was also evaluated in carotid bifurcation through a Western blotting assay. RESULTS: At 30 d of age, unanesthetized LP rats exhibited enhanced resting Rf (P = 0.001) and similar ABP and HR compared with the NP rats. Despite their similar baseline ABP values, LP rats exhibited augmented low-frequency variability (â¼91%; P = 0.01). In addition, the unanesthetized LP rats showed enhanced pressor (P = 0.01) and tachypnoeic (P = 0.03) responses to peripheral chemoreflex activation. The LP rats displayed elevated baseline tSN activity (â¼86%; P = 0.02) and PN burst frequency (45%; P = 0.01) and amplitude (53%; P = 0.001) as well as augmented sympathetic (P = 0.01) and phrenic (P = 0.04) excitatory responses to peripheral chemoreflex activation compared with the NP group. Furthermore, LP rats showed an increase of â¼100% in HIF-1α protein density in carotid bifurcation compared with NP rats. CONCLUSION: Sympathetic-respiratory overactivity and amplified peripheral chemoreceptor responses, potentially through HIF-1α-dependent mechanisms, precede the onset of hypertension in juvenile rats exposed to protein undernutrition during gestation and lactation.
Assuntos
Células Quimiorreceptoras/metabolismo , Dieta com Restrição de Proteínas/efeitos adversos , Fenômenos Fisiológicos da Nutrição Materna , Sistema Nervoso Periférico/fisiopatologia , Pré-Hipertensão/fisiopatologia , Sistema Respiratório/fisiopatologia , Sistema Nervoso Simpático/fisiopatologia , Animais , Peso ao Nascer , Artéria Carótida Primitiva/metabolismo , Artéria Carótida Primitiva/patologia , Artéria Carótida Primitiva/fisiopatologia , Células Quimiorreceptoras/patologia , Feminino , Desenvolvimento Fetal , Retardo do Crescimento Fetal/etiologia , Retardo do Crescimento Fetal/fisiopatologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Lactação , Masculino , Sistema Nervoso Periférico/patologia , Nervo Frênico/patologia , Nervo Frênico/fisiopatologia , Gravidez , Pré-Hipertensão/etiologia , Pré-Hipertensão/metabolismo , Pré-Hipertensão/patologia , Ratos Wistar , Sistema Respiratório/patologia , Sistema Nervoso Simpático/patologia , Nervos Torácicos/patologia , Nervos Torácicos/fisiopatologiaRESUMO
BACKGROUND: Study suggested that elevated homocysteine showed a multiplicative effect on cardiovascular diseases in hypertensive subjects. It was reported that elevated homocysteine level was independently associated with increased arterial stiffness in prehypertensives. It remains unclear whether prehypertensives combined with elevated homocysteine have adverse cardiovascular risk factors. We aimed to compare cardiometabolic risk profile between prehypertensives with hyperhomocysteinaemia and those without either condition. METHODS: Plasma total homocysteine and risk profile were determined among 874 Chinese non-hypertension individuals in Tianjin. They were subdivided into four groups: prehypertension with hyperhomocysteinaemia (≥10 µmol/L), prehypertension with normal homocysteine (<10 µmol/L), normotension with hyperhomocysteinaemia, normotension with normol homocysteine, respectively. RESULTS: In 874 participants, 22.5% of them were male, mean age was 56.8 years. In multiple comparisons, after adjustment for age, gender, smoking, alcohol, exercise, education prehypertensives had higher body mass index (BMI) and high sensitive C reactive protein (hs-CRP) than normotensives (p < 0.05, respectively); Only prehypertensive subjects with hyperhomocysteinaemia had higher triglyceride and serum uric acid compared to normotensive subjects, and lower HDL cholesterol than normotensives with normal homocysteine (p < 0.05, respectively). However, the significance of higher hs-CRP, uric acid and lower HDL cholesterol were abolished when further adjustment was made for BMI. CONCLUSION: The combination of prehypertension and hyperhomocusteinaemia increases the likelihood of having adverse cardiometabolic risk profile. Strict lipid management and weigh control may be needed in prehypertensives with elevated homocysteine.
Assuntos
Doenças Cardiovasculares , Hiper-Homocisteinemia , Pré-Hipertensão , Pressão Sanguínea , Índice de Massa Corporal , Proteína C-Reativa/análise , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/prevenção & controle , China/epidemiologia , Dislipidemias/complicações , Dislipidemias/metabolismo , Feminino , Humanos , Hiper-Homocisteinemia/complicações , Hiper-Homocisteinemia/diagnóstico , Hiper-Homocisteinemia/metabolismo , Masculino , Pessoa de Meia-Idade , Vigilância da População , Pré-Hipertensão/diagnóstico , Pré-Hipertensão/etiologia , Pré-Hipertensão/metabolismo , Fatores de RiscoRESUMO
Adulthood hypertension can be programmed in response to a suboptimal environment in early life. However, developmental plasticity also implies that one can prevent hypertension in adult life by administrating appropriate compounds during early development. We have termed this reprogramming. While the risk of hypertension has been assessed in many mother-child cohorts of human developmental programming, interventions necessary to prove causation and provide a reprogramming strategy are lacking. Since the developing kidney is particularly vulnerable to environmental insults and blood pressure is determined by kidney function, renal programming is considered key in developmental programming of hypertension. Common pathways, whereby both genetic and acquired developmental programming converge into the same phenotype, have been recognized. For instance, the same reprogramming interventions aimed at shifting nitric oxide (NO)-reactive oxygen species (ROS) balance, such as perinatal citrulline or melatonin supplements, can be protective in both genetic and developmentally programmed hypertension. Furthermore, a significantly increased expression of gene Ephx2 (soluble epoxide hydrolase) was noted in both genetic and acquired animal models of hypertension. Since a suboptimal environment is often multifactorial, such common reprogramming pathways are a practical finding for translation to the clinic. This review provides an overview of potential clinical applications of reprogramming strategies to prevent programmed hypertension. We emphasize the kidney in the following areas: mechanistic insights from human studies and animal models to interpret programmed hypertension; identified risk factors of human programmed hypertension from mother-child cohorts; and the impact of reprogramming strategies on programmed hypertension from animal models. It is critical that the observed effects on developmental reprogramming in animal models are replicated in human studies.
Assuntos
Hipertensão/prevenção & controle , Rim/metabolismo , Animais , Anti-Hipertensivos/uso terapêutico , Epóxido Hidrolases/metabolismo , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/metabolismo , Pré-Hipertensão/tratamento farmacológico , Pré-Hipertensão/metabolismo , Espécies Reativas de Oxigênio/metabolismoRESUMO
OBJECTIVE: To explore electro-acupuncture's (EA's) effect on gene expression in heart of rats with stress-induced pre-hypertension and try to reveal its biological mechanism based on gene chip technology. METHODS: Twenty-seven Wistar male rats were randomly divided into 3 groups. The stress-induced hypertensive rat model was prepared by electric foot-shocks combined with generated noise. Molding cycle lasted for 14 days and EA intervene was applied,on rats in model + EA group during model preparation. Rat Gene 2.0 Sense Target Array technology was used for the determination of gene expression profiles and the screened key genes were verified by real-time quantitative polymerase chain reaction (RT-PCR) method. RESULTS: Compared with blank control group, 390 genes were changed in model group; compared with model control group, 330 genes were changed in model+EA group. Significance analysis of gene function showed that the differentially expressed genes are those involved in biological process, molecular function and cellular components. RT-PCR result of the screened key genes is consistent with that of gene chip test. CONCLUTION: EA could significantly lower blood pressure of stress-induced pre-hypertension rats and affect its gene expression profile in heart. Genes that related to the contraction of vascular smooth muscle may be involved in EA's anti-hypertensive mechanism.
Assuntos
Eletroacupuntura , Pré-Hipertensão/terapia , Animais , Pressão Sanguínea , Expressão Gênica , Coração/fisiopatologia , Humanos , Masculino , Miocárdio/metabolismo , Análise de Sequência com Séries de Oligonucleotídeos , Pré-Hipertensão/genética , Pré-Hipertensão/metabolismo , Pré-Hipertensão/fisiopatologia , Ratos , Ratos WistarRESUMO
Little information is available on temporal trends in sodium intake in the U.S. population using urine sodium excretion as a biomarker. Our aim was to assess 1988-2010 trends in estimated 24-h urine sodium (24hUNa) excretion among U.S. adults (age 20-59 y) participating in the cross-sectional NHANES. We used subsamples from a 1988-1994 convenience sample, a 2003-2006 one-third random sample, and a 2010 one-third random sample to comply with resource constraints. We estimated 24hUNa excretion from measured sodium concentrations in spot urine samples by use of calibration equations (for men and women) derived from the International Cooperative Study on Salt, Other Factors, and Blood Pressure study. Estimated 24hUNa excretion increased over the 20-y period [1988-1994, 2003-2006, and 2010; means ± SEMs (n): 3160 ± 38.4 mg/d (1249), 3290 ± 29.4 mg/d (1235), and 3290 ± 44.4 mg/d (525), respectively; P-trend = 0.022]. We observed significantly higher mean estimated 24hUNa excretion in each survey period (P < 0.001) for men compared with women (31-33%) and for persons with a higher body mass index (BMI; 32-35% for obese vs. normal weight) or blood pressure (17-26% for hypertensive vs. normal blood pressure). After adjusting for age, sex, and race-ethnicity, temporal trends in mean estimated 24hUNa excretion remained significant (P-trend = 0.004). We observed no temporal trends in mean estimated 24hUNa excretion among BMI subgroups, nor after adjusting for BMI. Although several limitations apply to this analysis (the use of a convenience sample in 1988-1994 and using estimated 24hUNa excretion as a biomarker of sodium intake), these first NHANES data suggest that mean estimated 24hUNa excretion increased slightly in U.S. adults over the past 2 decades, and this increase may be explained by a shift in the distribution of BMI.
Assuntos
Hipertensão/epidemiologia , Hipertensão/metabolismo , Inquéritos Nutricionais/estatística & dados numéricos , Cloreto de Sódio na Dieta/urina , Adulto , Pressão Sanguínea , Índice de Massa Corporal , Estudos Transversais , Feminino , Inquéritos Epidemiológicos , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/epidemiologia , Obesidade/metabolismo , Pré-Hipertensão/epidemiologia , Pré-Hipertensão/metabolismo , Distribuição por Sexo , Estados Unidos/epidemiologia , Adulto JovemRESUMO
The birdseed Phalaris canariensis (Pc) is popularly used as an antihypertensive agent. The aqueous extract of Pc (AEPc) was administered in adult normotensive Wistar rats and spontaneously hypertensive rats (SHR) and in prehypertensive young SHR (SHR(Y), 3 weeks old). Animals received AEPc (400 mg·kg(-1)·day(-1), by gavage) for 30 days, then groups were divided into 2 subgroups: one was treated for another 30 days and the other received water instead of AEPc for 30 days. AEPc reduced systolic blood pressure (SBP) in both adult groups; however, treatment interruption was followed by a gradual return of the SBP to baseline levels. SHR(Y) became hypertensive 30 days after weaning. AEPc minimized the increase in SBP in SHR(Y), but blood pressure rose to levels similar to those in the untreated group with treatment interruption. There were no changes in renal function, diuresis, or Na(+) excretion. Pc is rich in tryptophan, and the inhibition of the metabolism of tryptophan to kynurenine, a potential vasodilator factor, prevented the blood pressure reducing effect of AEPc. Moreover, AEPc significantly reduced sympathoexcitation. Data indicate that the metabolic derivative of tryptophan, kynurenine, may be a mediator of the volume-independent antihypertensive effect of Pc, which was at least in part mediated by suppression of the sympathetic tonus.
Assuntos
Anti-Hipertensivos/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Phalaris , Extratos Vegetais/farmacologia , Pré-Hipertensão/tratamento farmacológico , Animais , Anti-Hipertensivos/isolamento & purificação , Anti-Hipertensivos/metabolismo , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Hipertensão/metabolismo , Hipertensão/fisiopatologia , Cinurenina/metabolismo , Masculino , Phalaris/química , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/metabolismo , Pré-Hipertensão/metabolismo , Pré-Hipertensão/fisiopatologia , Ratos , Ratos Endogâmicos SHR , Ratos Wistar , Sistema Nervoso Simpático/efeitos dos fármacos , Sistema Nervoso Simpático/fisiopatologia , Fatores de Tempo , Triptofano/metabolismoRESUMO
Although recently the incidence of prehypertension has increased considerably, the pathophysiological mechanisms and the effects of gender in its causation have not yet been fully elucidated. Therefore, in this study body mass index (BMI), waist-hip ratio (WHR), basal heart rate (BHR), blood pressure (BP), rate pressure product (RPP), and spectral indices of heart rate variability (HRV) were reordered and analyzed in normotensive and prehypertensive males and females. It was observed that low frequency-high frequency (LF-HF) ratio, the sensitive indicator of sympathovagal imbalance (SVI), is significantly more (P < .001) in male prehypertensives compared with female prehypertensives. Although SVI in prehypertensives was found to be due to both sympathetic activation and vagal inhibition, contribution of vagal withdrawal was prominent in males. The LF-HF ratio was significantly correlated with BMI, WHR, BHR, BP, and RPP, which was more prominent in male prehypertensives and the degree of correlation was more for WHR and diastolic pressure. It was concluded that vagal inhibition plays an important role in critical alteration of SVI in the genesis of prehypertension, especially in males, and WHR could be a better indicator of SVI in prehypertensives. It was suggested that prehypertensives should improve their vagal tone to restore the sympathovagal homeostasis.
Assuntos
Doenças do Sistema Nervoso Autônomo/fisiopatologia , Pré-Hipertensão/fisiopatologia , Caracteres Sexuais , Doenças do Nervo Vago/fisiopatologia , Adulto , Doenças do Sistema Nervoso Autônomo/metabolismo , Pressão Sanguínea/fisiologia , Peso Corporal/fisiologia , Metabolismo Energético/fisiologia , Feminino , Frequência Cardíaca/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Inibição Neural/fisiologia , Pré-Hipertensão/metabolismo , Sistema Nervoso Simpático/fisiologia , Nervo Vago/fisiologia , Doenças do Nervo Vago/metabolismo , Relação Cintura-QuadrilRESUMO
The essential hypertension has been associated with membrane cell damage. The aim of the present study is investigate the relationship between erythrocyte Na(+),K(+)-ATPase and lipoperoxidation in prehypertensive patients compared to normotensive status. The present study involved the prehypertensive patients (systolic: 136 ± 7 mmHg; diastolic: 86.8 ± 6.3 mmHg; n = 8) and healthy men with normal blood pressure (systolic: 110 ± 6.4 mmHg; diastolic: 76.1 ± 4.2 mmHg; n = 8) who were matched for age (35 ± 4 years old). The venous blood samples of antecubital vein (5 mL) were collected into a tube containing sodium heparin as anticoagulant (1000 UI), and erythrocyte ghosts were prepared for quantifying Na(+),K(+)-ATPase activity. The extent of the thiobarbituric acid reactive substances (TBARS) was determined in plasma. The statistical analysis was carried out by Student's t-test and Pearson's correlation coefficient. A P < 0.05 was considered significant. The Na(+),K(+)-ATPase activity was lower in prehypertensive patients compared with normotensive subjects (4.9 versus 8.0 nmol Pi/mg protein/min; P < 0.05). The Na(+),K(+)-ATPase activity correlated negatively with TBARS content (r = -0.6; P < 0.05) and diastolic blood pressure (r = -0.84; P < 0.05). The present study suggests that Na(+),K(+)-ATPase activity reduction and elevation of the TBARS content may underlie the pathophysiological aspects linked to the prehypertensive status.
Assuntos
Eritrócitos/enzimologia , Pré-Hipertensão/sangue , ATPase Trocadora de Sódio-Potássio/sangue , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Estudos de Casos e Controles , Humanos , Masculino , Pré-Hipertensão/enzimologia , Pré-Hipertensão/metabolismoRESUMO
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.
Assuntos
Células Progenitoras Endoteliais , Pré-Hipertensão , Humanos , Células Progenitoras Endoteliais/metabolismo , Pré-Hipertensão/metabolismo , Endotélio Vascular/metabolismo , Estresse Mecânico , Receptores CXCR4/metabolismo , Transdução de Sinais , Células CultivadasRESUMO
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.
Assuntos
Angiotensina II/metabolismo , Angiotensina I/metabolismo , Enzima de Conversão de Angiotensina 2/metabolismo , Hipertensão , Condicionamento Físico Animal , Pré-Hipertensão , Animais , Pressão Sanguínea , Hipertensão/metabolismo , Hipertensão/terapia , Masculino , Estresse Oxidativo/fisiologia , Núcleo Hipotalâmico Paraventricular , Condicionamento Físico Animal/fisiologia , Pré-Hipertensão/metabolismo , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKYRESUMO
BACKGROUND: Neutrophil elastase level/activity is elevated in a variety of diseases such as atherosclerosis, systolic hypertension and obstructive pulmonary disease. It is unknown whether obese individuals with prehypertension also have elevated neutrophil elastase, and if so, whether it has a deleterious effect on pulmonary function. OBJECTIVES: To determine neutrophil elastase levels in obese prehypertensive women and investigate correlations with pulmonary function tests. METHODS: Thirty obese prehypertensive women were compared with 30 obese normotensive subjects and 30 healthy controls. The study groups were matched for age. MEASUREMENTS: The following were determined: body mass index, waist circumference, blood pressure, lipid profile, high sensitivity C-reactive protein, serum neutrophil elastase, and pulmonary function tests including forced expiratory volume in one second (FEV1), forced vital capacity (FVC) and FEV1/FVC ratio. RESULTS: Serum neutrophil elastase concentration was significantly higher in both prehypertensive (405.8 ± 111.6 ng/ml) and normotensive (336.5 ± 81.5 ng/ml) obese women than in control non-obese women (243.9 ± 23.9 ng/ml); the level was significantly higher in the prehypertensive than the normotensive obese women. FEV1, FVC and FEV1/FVC ratio in both prehypertensive and normotensive obese women were significantly lower than in normal controls, but there was no statistically significant difference between the prehypertensive and normotensive obese women. In prehypertensive obese women, there were significant positive correlations between neutrophil elastase and body mass index, waist circumference, systolic blood pressure, diastolic blood pressure, total cholesterol, triglyceride, low density lipoprotein cholesterol, high sensitivity C-reactive protein and negative correlations with high density lipoprotein cholesterol, FEV1, FVC and FEV1/FVC. CONCLUSION: Neutrophil elastase concentration is elevated in obese prehypertensive women along with an increase in high sensitivity C-reactive protein which may account for dyslipidemia and airflow dysfunction in the present study population.
Assuntos
Elastase de Leucócito/sangue , Obesidade/enzimologia , Pré-Hipertensão/enzimologia , Ventilação Pulmonar/fisiologia , Saúde da Mulher , Adulto , Biomarcadores/metabolismo , Índice de Massa Corporal , Proteína C-Reativa/metabolismo , Feminino , Volume Expiratório Forçado , Humanos , Pessoa de Meia-Idade , Obesidade/complicações , Obesidade/metabolismo , Pré-Hipertensão/complicações , Pré-Hipertensão/metabolismo , Fatores de RiscoRESUMO
AIM: to investigate the effect of consumption of dark chocolate 30 g/day for fifteen days on Nitric oxide (NO) serum levels and blood pressure in male and female employees with prehypertension. METHODS: the study was a parallel randomized clinical trial. A total of thirty-two subjects was divided into two groups using block randomization. Sixteen subjects received 30 g/day dark chocolate and dietary counseling (treatment group) and the other 16 subjects received white chocolate 25 g/day and dietary counseling (control group) for fifteen days. Data collected in this study consisted of age, physical activity, body massa index, intake of energy, intake of sodium, and intake of polyphenol, NO serum levels and blood pressure. The measurement of NO serum levels was done in pre- and after- treatment, while blood pressure was assessed in pre- , during- and after- treatment. Statistical analysis was performed using independent t-test for normal distribution data and Mann-Whitney test for not normal distribution data, with the level of significancy of 5%. RESULTS: after 15 days treatment, NO serum level between treatment and control groups were significantly different 7.70 ± 3.84 vs 1.92(-0.79 ± 17.78) (p=0.001). Both groups had decreased systolic and diastolic blood pressure. Systolic blood pressure was different significantly between groups after treatment 120.64 ± 8.47 vs 131.19 ± 7.45 (p=0.001), while diastolic blood pressure was not significant 74.14 ± 6.30 vs 77.44 ± 10.29 (p=0.308). CONCLUSION: in prehypertension subjects, dark chocolate 30 g/day increased NOx serum levels and decreased systolic blood pressure after 15 days of treatment.