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CONTEXT: There are well-established interactions between the thyroid and the kidney. Thyroid hypofunction is associated with reduced renal plasma flow (RPF), and hypothyroidism is highly prevalent in chronic kidney disease; however, less is known about the thyroid-kidney axis in the euthyroid state. OBJECTIVE: This work aimed to study the association of thyroid function with renovascular parameters in a well-phenotyped cohort of euthyroid normotensive and hypertensive individuals. METHODS: This cross-sectional, multicenter study of the HyperPATH Consortium took place in 5 US and European academic institutions. A total of 789 individuals, aged 18 to 65 years, with serum thyrotropin (TSH) 0.4 to 5.5 mIU/L, participated; individuals with uncontrolled or secondary hypertension or on medication affecting the hypothalamus-pituitary-thyroid axis were excluded. Hemodynamic parameters including RPF, thyroid function testing, and the Thr92Ala deiodinase 2 (D2) polymorphism were assessed in the setting of a liberal and restricted salt diet. We searched for associations between thyroid function and renovascular parameters and accounted for confounding factors, such as older age, hypertension, and diabetes. RESULTS: Serum TSH was inversely associated with RPF assessed in the setting both of liberal and restricted salt diets. This association remained significant and independent when accounting for confounding factors, whereas free thyroxine index (fTI) and the Thr92Ala polymorphism, associated with lower D2 catalytic activity and disrupted thyroid hormone tissue availability, were not independently associated with RPF. Serum TSH remained an independent predictor of RPF on a liberal salt diet when the analysis was restricted to healthy young individuals. CONCLUSION: Serum TSH levels, but not fTI nor the Thr92Ala D2 polymorphism, were independently inversely associated with RPF in individuals of the HyperPATH Consortium. These findings suggest a direct interconnection between TSH and renovascular dynamics even with TSH within reference range, warranting further investigation.
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Hipotireoidismo/fisiopatologia , Insuficiência Renal Crônica/fisiopatologia , Fluxo Plasmático Renal , Glândula Tireoide/fisiopatologia , Tireotropina/sangue , Adolescente , Adulto , Idoso , Estudos de Coortes , Estudos Transversais , Dieta Hipossódica , Feminino , Hemodinâmica , Humanos , Hipertensão Renal/sangue , Hipertensão Renal/fisiopatologia , Sistema Hipotálamo-Hipofisário/fisiopatologia , Hipotireoidismo/sangue , Iodeto Peroxidase/genética , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/sangue , Testes de Função Tireóidea , Adulto JovemRESUMO
PURPOSE: To explore the cellular immune response of patients with resistant hypertension treated with renal denervation (RDN). METHODS AND RESULTS: Twenty-three patients were included and blood samples were obtained in six timings, pre and post procedure. Response was evaluated at six-months and one year and was observed in 69.6% and 82.6% of patients, respectively. Absolute values of HLA-DR+ double negative (DN) T cells were significantly lower in the group of 'responders' at one year, and interaction between the timings were found in three T cell subsets (T CD4, T CD8 and naïve T CD8 cells), with the 'responders' tending to present with lower absolute values and little inter-timing variation. CONCLUSIONS: 'Responders' significantly present with lower absolute values of activated DN T cells and have lower and more stable values of total T CD8+, CD4+, and naïve T CD8+ cells. These cell types may be able to predict response to RDN.
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Hipertensão Renal/imunologia , Subpopulações de Linfócitos T/imunologia , Adulto , Idoso , Pressão Sanguínea , Ablação por Cateter , Citocinas/sangue , Denervação , Feminino , Artéria Femoral/cirurgia , Humanos , Hipertensão Renal/sangue , Hipertensão Renal/fisiopatologia , Hipertensão Renal/cirurgia , Rim/inervação , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoAssuntos
Glicemia/metabolismo , Endotélio Vascular/metabolismo , Hipertensão Essencial/complicações , Hipertensão Renal/etiologia , Mediadores da Inflamação/sangue , Lipídeos/sangue , Nefrite/etiologia , Biomarcadores/sangue , Pressão Sanguínea , Progressão da Doença , Endotélio Vascular/fisiopatologia , Hipertensão Essencial/sangue , Hipertensão Essencial/fisiopatologia , Feminino , Humanos , Hipertensão Renal/sangue , Hipertensão Renal/fisiopatologia , Masculino , Pessoa de Meia-Idade , Nefrite/sangue , Nefrite/fisiopatologia , Estresse Oxidativo , Medição de Risco , Fatores de Risco , Fatores de TempoRESUMO
Chemerin and its receptor, chemokine-like receptor 1 (CmklR1), are associated with chemotaxis, inflammation, and endothelial function, especially in metabolic syndrome, coronary heart disease, and hypertension. In humans, circulating chemerin levels and renal function show an inverse relation. So far, little is known about the potential role of chemerin in hypertensive nephropathy and renal inflammation. Therefore, we determined systemic and renal chemerin levels in 2-kidney-1-clip (2k1c) hypertensive and Thy1.1 nephritic rats, respectively, to explore the correlation between chemerin and markers of renal inflammation and fibrosis. Immunohistochemistry revealed a model-specific induction of chemerin expression at the corresponding site of renal damage (tubular vs. glomerular). In both models, renal expression of chemerin (RT-PCR, Western blot) was increased and correlated positively with markers of inflammation and fibrosis. In contrast, circulating chemerin levels remained unchanged. Taken together, these findings demonstrate that renal chemerin expression is associated with processes of inflammation and fibrosis-related to renal damage. However, its use as circulating biomarker of renal inflammation seems to be limited in our rat models.
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Quimiocinas/metabolismo , Glomerulonefrite/metabolismo , Hipertensão Renal/metabolismo , Inflamação/metabolismo , Rim/metabolismo , Rim/patologia , Nefrite/metabolismo , Animais , Biomarcadores/sangue , Biomarcadores/metabolismo , Quimiocinas/sangue , Quimiocinas/genética , Colágeno Tipo IV/metabolismo , Modelos Animais de Doenças , Fibrose , Glomerulonefrite/complicações , Glomerulonefrite/patologia , Hipertensão/sangue , Hipertensão/complicações , Hipertensão Renal/sangue , Hipertensão Renal/complicações , Hipertensão Renal/patologia , Inflamação/sangue , Inflamação/patologia , Rim/lesões , Macrófagos/patologia , Nefrite/sangue , Nefrite/complicações , Nefrite/patologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores de Quimiocinas/genética , Receptores de Quimiocinas/metabolismoRESUMO
Background and Objectives: Diabetes mellitus (DM) and hypertension (HT) are characterized by cell damage caused by inflammatory and metabolic mechanisms induced by alteration in reduction-oxidative status. Serum advanced oxidation protein products (AOPP) are new markers of protein damage induced by oxidative stress. We evaluated serum levels of AOPP in a cohort of patients with DM and HT, with or without renal complications, compared with a control healthy population. Materials and Methods: The study group comprised of 62 patients with type 2 DM and 56 with HT. The 62 patients affected by DM were further distinguished in 24 subjects without renal impairment, 18 with diabetic nephropathy (DN), 20 with chronic kidney disease (CKD) stage 2-3 secondary to DN. The subgroup of 56 patients with primary HT comprised 26 subjects without renal complications and 30 with CKD (stage 2-3) secondary to HT. Thirty healthy controls, matched for age and sex, were recruited among blood donors. Results: Increased AOPP levels were found in DM patients compared with healthy subjects, although not significantly. This index was higher and more significant in patients with DN and CKD secondary to DN than in DM patients without nephropathy (p < 0.05) or controls (p < 0.0001). Patients with HT and with kidney impairment secondary to HT also had significantly higher AOPP serum levels than controls (p < 0.01 and p < 0.0001, respectively). There were no significant differences in mean AOPP levels among DM and HT patients. Conclusion: Our study showed that oxidative stress was higher in diabetic or hypertensive subjects than in healthy controls and, in particular, it appeared to be more severe in patients with renal complications. We suggest that the assessment of AOPP in diabetic and hypertensive patients may be important to predict the onset of renal failure and to open a new perspective on the adoption of antioxidant molecules to prevent CKD in those settings.
Assuntos
Produtos da Oxidação Avançada de Proteínas/análise , Nefropatias Diabéticas/classificação , Hipertensão Renal/classificação , Nefrite/classificação , Adulto , Produtos da Oxidação Avançada de Proteínas/sangue , Idoso , Estudos de Coortes , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/fisiopatologia , Nefropatias Diabéticas/sangue , Nefropatias Diabéticas/fisiopatologia , Feminino , Humanos , Hipertensão Renal/sangue , Hipertensão Renal/fisiopatologia , Itália , Masculino , Pessoa de Meia-Idade , Nefrite/sangue , Nefrite/fisiopatologia , Estresse OxidativoRESUMO
BACKGROUND We assessed levels of circulating amino acids in different etiologies of chronic kidney disease (CKD) and the association of amino acids with risk factors of CKD progression. MATERIAL AND METHODS High-performance liquid chromatography-based analysis was used to determine amino acid profiles in patients with diabetic nephropathy (DN, n=20), hypertensive nephropathy (HN, n=26), and chronic nephritis (CN, n=33), and in healthy controls (HC, n=25). RESULTS All 3 types of CKD patients displayed decreased serum levels of serine, glycine, GABA, and tryptophan compared with healthy controls. Moreover, serine and tryptophan were positively correlated with glucose in DN cohorts. Total cholesterol was positively correlated with tryptophan levels in the DN cohort and negatively correlated with serine levels in the CN cohort. In the HN cohort, glycine was negatively correlated with triglyceride levels, and systolic blood pressure (SBP) was negatively correlated with GABA levels. CONCLUSIONS Patients with different etiologies of CKD have significantly different amino acids profiles, and this indicates specific supplementary nutritional needs in CKD patients.
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Nefropatias Diabéticas/metabolismo , Hipertensão Renal/metabolismo , Nefrite/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Aminoácidos/análise , Aminoácidos/sangue , China , Cromatografia Líquida de Alta Pressão/métodos , Doença Crônica , Estudos de Coortes , Nefropatias Diabéticas/sangue , Progressão da Doença , Feminino , Taxa de Filtração Glomerular , Glomerulonefrite/complicações , Humanos , Hipertensão Renal/sangue , Masculino , Pessoa de Meia-Idade , Nefrite/sangue , Fenótipo , Prognóstico , Insuficiência Renal Crônica/etiologia , Insuficiência Renal Crônica/fisiopatologia , Fatores de RiscoRESUMO
Although angiotensin II (AngII) is known to cause renal injury and fibrosis, the underlying mechanisms remain poorly characterized. Here we show that hypertensive nephropathy (HN) patients and AngII-infused mice exhibit elevated levels of circulating miR103a-3p. We observe a positive correlation between miR-103a-3p levels and AngII-induced renal dysfunction. miR-103a-3p suppresses expression of the sucrose non-fermentable-related serine/threonine-protein kinase SNRK in glomerular endothelial cells, and glomeruli of HN patients and AngII-infused mice show reduced endothelial expression of SNRK. We find that SNRK exerts anti-inflammatory effects by interacting with activated nuclear factor-κB (NF-κB)/p65. Overall, we demonstrate that AngII increases circulating miR-103a-3p levels, which reduces SNRK levels in glomerular endothelial cells, resulting in the over-activation of NF-κB/p65 and, consequently, renal inflammation and fibrosis. Together, our work identifies miR-103a-3p/SNRK/NF-κB/p65 as a regulatory axis of AngII-induced renal inflammation and fibrosis.
Assuntos
Angiotensina II/metabolismo , Glomerulonefrite/patologia , Hipertensão Renal/patologia , Glomérulos Renais/patologia , MicroRNAs/metabolismo , Nefrite/patologia , Proteínas Serina-Treonina Quinases/genética , Adulto , Angiotensina II/administração & dosagem , Animais , Estudos de Casos e Controles , Células Cultivadas , Modelos Animais de Doenças , Feminino , Fibrose , Glomerulonefrite/sangue , Glomerulonefrite/genética , Glomerulonefrite/urina , Voluntários Saudáveis , Humanos , Hipertensão Renal/sangue , Hipertensão Renal/genética , Hipertensão Renal/urina , Glomérulos Renais/citologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , MicroRNAs/sangue , MicroRNAs/urina , Pessoa de Meia-Idade , Nefrite/sangue , Nefrite/genética , Nefrite/urina , Cultura Primária de Células , Proteínas Serina-Treonina Quinases/metabolismo , Fator de Transcrição RelA/metabolismoRESUMO
INTRODUCTION: Hypertension is regarded as a condition of mild inflammation and endothelial imbalance. The aim of the study was to evaluate serum concentrations of biomarkers of inflammation and endothelial function: tumour necrosis factor alpha (TNF-α), endothelin-1 (ET-1), and N-terminal fragment of pro-atrial natriuretic peptide (NTpro-ANP) in hypertensive and normotensive children. MATERIAL AND METHODS: We studied 63 children aged 13.56 ± 3.73 years, divided into two groups: a group with primary hypertension (n = 50) and a group with renal hypertension (n = 13). The control group consisted of 34 normotensive children aged 12.76 ± 3.96 years. Biomarkers were measured with ELISA tests. RESULTS: ET-1 levels were significantly higher in primary hypertension (9.93 ± 1.73 pg/ml) and renal hypertension (10.77 ± 1.50 pg/ml) in comparison to controls (4.03 ± 0.97 pg/ml), (p < 0.001, p < 0.001, respectively). NT-pro ANP concentrations in primary hypertension (71.03 ± 10.02 pg/ml), and renal hypertension (84.78 ± 6.44 pg/ml) were significantly higher than in the control group (29.62 ± 5.56 pg/ml) (p < 0.001, p < 0.001, respectively). TNF-α concentrations in primary hypertension (8.36 ± 1.60 pg/ml) and renal hypertension (7.35 ± 0.93 pg/ml) significantly exceeded concentrations in controls (4.49 ± 0.93 pg/ml), (p < 0.001, p < 0.001, respectively). ET-1 and NT-pro ANP concentrations in renal hypertension significantly exceeded those in primary hypertension (p = 0.049, p < 0.001, respectively) while TNF-α levels in renal hypertension were significantly lower than in primary hypertension (p = 0.046). CONCLUSIONS: The results of our study show that ET-1, NT-pro ANP, and TNF-a concentrations are increased in hypertension in children. Our investigation indicates significant importance of inflammation and endothelial involvement in hypertension in youth.
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Fator Natriurético Atrial/sangue , Endotelina-1/sangue , Hipertensão Essencial/sangue , Hipertensão Renal/sangue , Fator de Necrose Tumoral alfa/sangue , Adolescente , Biomarcadores/sangue , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Fragmentos de Peptídeos/sangueRESUMO
Cirsium japonicum, a constituent of traditional Chinese medicine, has been shown to exert inflammatory effects as well as to improve the circulation and thus to counteract hematologic stasis. Studies have demonstrated that intermedin (IMD) has protective effects on hypertension in rats by regulating the Ang/NO metabolic pathway. In this study, we investigated whether by regulating the expression of IMD, Cirsium japonicum could improve cardiac function in rats with 2k1c-induced renal hypertension. Renal hypertension was induced in Sprague-Dawley rats by occluding the renal artery. The rats were maintained on a normal diet and randomly divided into four groups: sham, 2k1c, 2k1c with Cirsium japonicum (1.8â¯g/kg per day) and 2k1c with IMD (nâ¯=â¯10 in each group). Cardiac function, plasma angiotensin II (Ang II), IMD, serum nitric oxide (NO) and nitric oxide synthase (NOS), as well as the expression of IMD and adrenomedullin (ADM) in the aorta and left ventricle were analyzed. Administration of Cirsium japonicum or IMD significantly strengthened cardiac function in 2k1c-induced rats, increased serum NO and NOS levels, reduced plasma Ang II, and upregulated IMD expression in the aorta and left ventricle. These results demonstrate that Cirsium japonicum has cardioprotective effects on 2k1c-induced renal hypertension in rats via the IMD/NO pathway.
Assuntos
Adrenomedulina/sangue , Cirsium , Hipertensão Renal/sangue , Neuropeptídeos/sangue , Óxido Nítrico/sangue , Extratos Vegetais/uso terapêutico , Função Ventricular Esquerda/fisiologia , Animais , Aorta/efeitos dos fármacos , Aorta/fisiologia , Hipertensão Renal/tratamento farmacológico , Hipertensão Renal/fisiopatologia , Masculino , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Função Ventricular Esquerda/efeitos dos fármacosRESUMO
OBJECTIVES: Identification of factors that contribute to urinary albumin losses in hypertensive nephropathy is crucial for prevention of renal deterioration. The aim of this study was to investigate the relationship of low-grade albuminuria with plasma aldosterone levels in treatment-naïve hypertensive patients free of additional comorbidities that might affect renal function. METHODS: In 242 newly diagnosed patients with uncomplicated primary hypertension, we obtained duplicate 24-h urine collections for measurement of urinary albumin/creatinine ratio (UACR) and measured plasma aldosterone levels. Patients with diabetes, overt proteinuria (>300âmg/day), glomerular filtration rate less than 30âml/min per 1.73âm, and previous renal diseases were excluded. RESULTS: Increasing UACR was associated with significantly and progressively higher blood pressure (BP), HDL-cholesterol, and plasma aldosterone levels, and with lower glomerular filtration. Microalbuminuria (30-300âmg/day) was detected in 41 (17%) of 242 hypertensive patients, and these patients had significantly higher BP and plasma aldosterone levels (178â±â113 vs. 128â±â84âpg/ml; Pâ=â0.001), and lower glomerular filtration than patients without microalbuminuria. UACR was directly and independently correlated with BP and plasma aldosterone levels. In a logistic regression model, presence of microalbuminuria was associated with plasma aldosterone levels independently of glomerular filtration and demographic, anthropometric, and metabolic variables. CONCLUSION: In nondiabetic, treatment-naïve patients with hypertension, low-grade albuminuria is independently associated with elevated plasma aldosterone. These findings suggest a contribution of aldosterone to the early glomerular changes occurring in hypertensive nephropathy.
Assuntos
Albuminúria/sangue , Aldosterona/sangue , Hipertensão Renal/sangue , Hipertensão/sangue , Nefrite/sangue , Adulto , Idoso , Albuminúria/complicações , Albuminúria/fisiopatologia , Feminino , Humanos , Hipertensão/complicações , Hipertensão/fisiopatologia , Hipertensão Renal/complicações , Rim/fisiopatologia , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Nefrite/complicaçõesRESUMO
BACKGROUND/AIMS: Serum cortisol level is elevated in patients with essential hypertension. We aimed at investigating the association of serum cortisol levels with parameters of renal function in essential hypertension. METHODS: One hundred and seventy-eight patients with essential hypertension participated in the study. Fasting serum samples were collected at 8:00 am. Renal function was measured as estimated glomerular filtration rate (eGFR) calculated by the Chronic Kidney Disease Epidemiology Collaboration creatinine- cystatin C equation (eGFRcr-cys). Correlation analysis and stepwise regression analysis were used to detect the relationship between cortisol and eGFRcr-cys. The distributions of serum cortisol were split by the tertiles and subjects were stratified into those with low, median and high levels accordingly. RESULTS: Serum cortisol levels were significantly higher in subjects whose eGFRcr-cys<90 ml/min/1.73 m2 than subjects whose eGFRcr-cys>90 ml/min/1.73 m2 (394.0±93.4 vs. 343.2±98.4 nmol/L, P=0.001). Age, systolic blood pressure, and serum total cholesterol, uric acid, cortisol levels were significantly associated with eGFRcr-cys, serum levels of creatinine and cystatin C. After adjusting for clinical factors, serum cortisol level had a statistically significant negative association with the eGFRcr-cys (ß=-0.19, P=0.027), and positive associations with cystatin C (ß=0.31, P=0.001) and creatinine (ß=0.14, P=0.044). With the increment of cortisol tertile, the eGFRcr-cys significantly decreased (93.18±14.36 vs. 84.61±14.67 vs. 81.29±12.36 ml/min/1.73 m2 for low, median and high tertile, respecively, P=0.001). CONCLUSION: Serum cortisol level was negatively correlated with eGFRcr-cys in subjects with essential hypertension. Further studies are needed to investigate whether cortisol plays a role in hypertensive nephropathy development.
Assuntos
Hidrocortisona/sangue , Hipertensão/sangue , Insuficiência Renal Crônica/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Hipertensão Essencial , Taxa de Filtração Glomerular , Humanos , Hidrocortisona/fisiologia , Hipertensão Renal/sangue , Pessoa de Meia-Idade , Nefrite/sangue , Insuficiência Renal Crônica/fisiopatologiaRESUMO
The aim of the present study was to investigate the protective effects of melatonin (MLT) on hypertension-induced renal injury and identify its mechanism of action. Twenty-four healthy male Wistar rats were divided into a sham control group (n=8), which was subjected to sham operation and received vehicle treatment (physiological saline intraperitoneally at 0.1 ml/100 g), a vehicle group (n=8), which was subjected to occlusion of the left renal artery and vehicle treatment, and the MLT group (n=8), which was subjected to occlusion of the left renal artery and treated with MLT (10 mg/kg/day). Pathological features of the renal tissues were determined using hematoxylin and eosin staining and Masson staining. Urine protein, serum creatinine (Scr), superoxide dismutase (SOD) and malondialdehyde (MDA) were determined. Immunohistochemical analysis was performed to determine the expression of heme oxygenase1 (HO1), intercellular adhesion molecule1 (ICAM1), inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS). Furthermore, reverse transcription polymerase chain reaction was conducted to determine the mRNA expression of HO1, ICAM1, eNOS and iNOS. A marked decrease in blood pressure was noticed in the MLT group at week 4 compared with that of the vehicle group (P<0.01). Furthermore, MLT treatment attenuated the infiltration of inflammatory cells and oedema/atrophy of renal tubules. MLT attenuated hypertension-induced increases in urine protein excretion, serum creatinine and MDA as well as decreases in SOD activity in renal tissues. Furthermore, MLT attenuated hypertension-induced increases in iNOS and ICAM1 as well as decreases in eNOS and HO1 expression at the mRNA and protein level. In conclusion, the results of the present study indicated that MLT had protective roles in hypertensioninduced renal injury. Its mechanism of action is, at least in part, associated with the inhibition of oxidative stress.
Assuntos
Hipertensão Renal/complicações , Nefropatias/etiologia , Melatonina/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Animais , Pressão Sanguínea/efeitos dos fármacos , Creatinina/sangue , Edema/complicações , Edema/patologia , Edema/fisiopatologia , Regulação da Expressão Gênica/efeitos dos fármacos , Heme Oxigenase-1/genética , Heme Oxigenase-1/metabolismo , Hipertensão Renal/sangue , Hipertensão Renal/fisiopatologia , Imuno-Histoquímica , Inflamação/sangue , Inflamação/complicações , Inflamação/patologia , Molécula 1 de Adesão Intercelular/genética , Molécula 1 de Adesão Intercelular/metabolismo , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Nefropatias/sangue , Nefropatias/fisiopatologia , Masculino , Malondialdeído/metabolismo , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Óxido Nítrico Sintase Tipo III/genética , Óxido Nítrico Sintase Tipo III/metabolismo , Proteinúria/sangue , Proteinúria/complicações , Proteinúria/fisiopatologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos Wistar , Superóxido Dismutase/metabolismoRESUMO
We investigated the involvement of cyclooxygenase-2 (COX-2) and the renin-angiotensin system in N(G)-nitro-L-arginine methyl ester (L-NAME)-induced hypertension. Male Wistar rats were treated with L-NAME (75.0 mg·(kg body mass)(-1)·day(-1), in their drinking water) for different durations (1-33 days). COX-2 and renin mRNA were measured using real-time PCR in the renal cortex, and prostanoids were assessed in the renal perfusate, whereas angiotensin II (Ang II) and Ang (1-7) were quantified in plasma. In some rats, nitric oxide synthase inhibition was carried out in conjunction with oral administration of captopril (30.0 mg·kg(-1)·day(-1)) or celecoxib (1.0 mg·kg(-1)·day(-1)) for 2 or 19 days. We found a parallel increase in renocortical COX-2 and renin mRNA starting at day 2 of treatment with L-NAME, and both peaked at 19-25 days. In addition, L-NAME increased renal 6-Keto-PGF(1α) (prostacyclin (PGI2) metabolite) and plasma Ang II from day 2, but reduced plasma Ang (1-7) at day 19. Captopril prevented the increase in blood pressure, which was associated with lower plasma Ang II and increased COX-2-derived 6-Keto-PGF(1α) at day 2 and plasma Ang (1-7) at day 19. Celecoxib partially prevented the increase in blood pressure; this effect was associated with a reduction in plasma Ang II. These findings indicate that renal COX-2 expression increased in parallel with renin expression, renal PGI2 synthesis, and plasma Ang II in L-NAME-induced hypertension.
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Ciclo-Oxigenase 2/metabolismo , Modelos Animais de Doenças , Regulação da Expressão Gênica , Hipertensão Renal/metabolismo , Córtex Renal/metabolismo , Renina/metabolismo , 6-Cetoprostaglandina F1 alfa/sangue , 6-Cetoprostaglandina F1 alfa/metabolismo , Angiotensina I/sangue , Angiotensina I/metabolismo , Angiotensina II/sangue , Angiotensina II/metabolismo , Animais , Anti-Hipertensivos/uso terapêutico , Captopril/uso terapêutico , Celecoxib/uso terapêutico , Ciclo-Oxigenase 2/química , Ciclo-Oxigenase 2/genética , Inibidores de Ciclo-Oxigenase 2/uso terapêutico , Regulação da Expressão Gênica/efeitos dos fármacos , Hipertensão Renal/sangue , Hipertensão Renal/prevenção & controle , Córtex Renal/efeitos dos fármacos , Córtex Renal/enzimologia , Masculino , NG-Nitroarginina Metil Éster , Óxido Nítrico/metabolismo , Fragmentos de Peptídeos/sangue , Fragmentos de Peptídeos/metabolismo , RNA Mensageiro/metabolismo , Distribuição Aleatória , Ratos Wistar , Renina/genéticaRESUMO
Chronic kidney disease (CKD) is an important public health problem. Patients with end-stage renal disease have a significant renalase deficiency, which could be one of the mechanisms explaining high prevalence of hypertension in these patients. The aim of this study was to investigate the possible association of renalase gene (rs2296545) polymorphism with normotensive and hypertensive CKD in sampled Egyptian patients and to determine the effect of such polymorphism on epinephrine level. Renalase gene (rs2296545) polymorphism was genotyped in 178 patients with CKD (83 normotensive and 95 hypertensive nephrosclerosis) and 178 normal healthy adults using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). Epinephrine level was measured by HPLC method. We found an association of renalase (rs2296545) CC genotype and C allele with CKD. Also, the epinephrine level was significantly increased in normotensive and hypertensive nephrosclerosis patients as compared to controls. CKD patients with CC genotype showed significant high epinephrine level as compared to CG and GG genotypes.
Assuntos
Predisposição Genética para Doença , Hipertensão Renal/genética , Falência Renal Crônica/genética , Monoaminoxidase/genética , Nefrite/genética , Polimorfismo de Nucleotídeo Único , Insuficiência Renal Crônica/genética , Adulto , Alelos , Estudos de Casos e Controles , Egito , Epinefrina/sangue , Feminino , Expressão Gênica , Humanos , Hipertensão Renal/sangue , Hipertensão Renal/diagnóstico , Hipertensão Renal/patologia , Falência Renal Crônica/sangue , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/patologia , Masculino , Pessoa de Meia-Idade , Monoaminoxidase/sangue , Nefrite/sangue , Nefrite/diagnóstico , Nefrite/patologia , Polimorfismo de Fragmento de Restrição , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/patologiaAssuntos
Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Hipertensão Renal/tratamento farmacológico , Falência Renal Crônica/complicações , Bloqueadores do Receptor Tipo 1 de Angiotensina II/efeitos adversos , Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Anti-Hipertensivos/efeitos adversos , Doença das Coronárias/sangue , Doença das Coronárias/complicações , Doença das Coronárias/tratamento farmacológico , Nefropatias Diabéticas/sangue , Nefropatias Diabéticas/complicações , Nefropatias Diabéticas/tratamento farmacológico , Quimioterapia Combinada , Humanos , Hipertensão Renal/sangue , Falência Renal Crônica/sangue , Falência Renal Crônica/tratamento farmacológico , Testes de Função Renal , Antagonistas de Receptores de Mineralocorticoides/efeitos adversos , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Renina/antagonistas & inibidores , Renina/sangueRESUMO
This study assessed the urinary albumin/creatinine ratio (ACR) and uric acid metabolism in 70 hypertensive patients with chronic kidney disease in whom urinary ACR had remained ≥30 mg/g under the treatment of the L-type calcium channel blocker amlodipine. Three months after switching to the N/L-type calcium channel blocker cilnidipine, blood pressure (BP) did not change; however, urinary ACR significantly decreased with cilnidipine. Serum uric acid levels showed no significant change. In cases where uric acid production had been high (urinary uric acid/creatinine ratio ≥0.5), the urinary uric acid/creatinine ratio decreased significantly after cilnidipine treatment, suggesting that cilnidipine can suppress excessive uric acid formation. These results suggest that switching from amlodipine to cilnidipine results in a significant reduction in urinary ACR as well as significant reduction in uric acid production. Thus, cilnidipine is more useful than amlodipine in improving albuminuria and uric acid metabolism in hypertensive patients with chronic kidney disease.
Assuntos
Bloqueadores dos Canais de Cálcio/uso terapêutico , Di-Hidropiridinas/uso terapêutico , Hipertensão Renal/tratamento farmacológico , Falência Renal Crônica/tratamento farmacológico , Ácido Úrico/sangue , Idoso , Idoso de 80 Anos ou mais , Albuminúria/sangue , Albuminúria/tratamento farmacológico , Anlodipino/efeitos adversos , Anlodipino/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Bloqueadores dos Canais de Cálcio/efeitos adversos , Creatinina/sangue , Estudos Cross-Over , Nefropatias Diabéticas/sangue , Nefropatias Diabéticas/tratamento farmacológico , Di-Hidropiridinas/efeitos adversos , Relação Dose-Resposta a Droga , Substituição de Medicamentos , Feminino , Humanos , Hipertensão Renal/sangue , Japão , Falência Renal Crônica/sangue , Masculino , Pessoa de Meia-Idade , Nefroesclerose/sangue , Nefroesclerose/tratamento farmacológicoRESUMO
BACKGROUND: Activated coagulation Factor XII (FXIIa) infusion increases peripheral resistance (TPR) and mean arterial pressure (MAP) of Brown Norway but not plasma kininogen deficient Brown Norway Katholiek (BNK) rats. FXIIa concentrations are elevated in hypertensive end-stage renal disease patients receiving conventional haemodialysis (CHD). Conversion to nocturnal haemodialysis (NHD) lowers peripheral resistance and MAP. OBJECTIVE: To determine whether the plasma coagulation FXIIa-kallikrein-kinin axis contributes to the hypertension of chronic kidney disease (CKD). METHODS: Plasma FXIIa and haemodynamic data were acquired in 11 CHD patients before and after 2 months of NHD. Cardiac and systemic haemodynamics of Brown Norway and BNK rats rendered hypertensive and uremic by 5/6 nephrectomy (NX) were determined before and after acute FXIIa inhibition. RESULTS: FXIIa was increased three-fold in CHD patients relative to control plasma (P < 0.05). After conversion to NHD, both ΔMAP and ΔTPR correlated with ΔFXIIa. In rats, plasma FXIIa was three-fold higher in both NX groups than respective SHAM controls (all P < 0.05), but MAP (147 ± 4 vs. 133 ± 2 mmHg; P < 0.05) and TPR (2.8 ± 0.2 vs. 2.3 ± 0.2 units; P < 0.05) were greater in Brown Norway NX (n = 16) than in BNK (n = 15) NX rats. FXIIa correlated with MAP only in Brown Norway NX, and plasma catecholamines were increased relative to SHAM only in Brown Norway NX (P < 0.05). In Brown Norway NX rats, FXIIa inhibitor infusion decreased MAP (-12 mmHg) and TPR (-0.5 Units) (both P < 0.05), and halved catecholamines (P < 0.05). No such changes occurred in BNK NX rats. CONCLUSION: FXIIa-kininogen mediated vasoconstriction contributes significantly to CKD hypertension in Brown Norway rats; this novel mechanism may be active in humans with CKD.
Assuntos
Fator XIIa/metabolismo , Hipertensão Renal/sangue , Hipertensão Renal/etiologia , Falência Renal Crônica/sangue , Falência Renal Crônica/complicações , Cininas/sangue , Adulto , Animais , Pressão Sanguínea/fisiologia , Modelos Animais de Doenças , Feminino , Humanos , Hipertensão Renal/fisiopatologia , Falência Renal Crônica/fisiopatologia , Masculino , Pessoa de Meia-Idade , Ratos , Ratos Endogâmicos BN , Diálise Renal , Resistência Vascular/fisiologia , Vasoconstrição/fisiologiaRESUMO
A soluble (pro)renin receptor (sPRR) circulates in plasma and is able to bind renin and prorenin. It is not known whether plasma sPRR concentrations vary with the activity of the renin-angiotensin system. We measured plasma sPRR, renin, prorenin, and aldosterone concentrations in 121 white and 9 black healthy subjects, 40 patients with diabetes mellitus, 41 hypertensive patients with or without renin-angiotensin system blockers, 9 patients with primary aldosteronism, and 10 patients with Gitelman syndrome. Median physiological plasma sPRR concentration was 23.5 ng/mL (interquartile range, 20.9-26.5) under usual uncontrolled sodium diet. sPRR concentration in healthy subjects, unlike renin and prorenin, did not display circadian variation or dependence on age, sex, posture, or hormonal status. sPRR concentrations were ≈25% lower in black than in white subjects, whereas renin concentrations were ≈40% lower. Patients with diabetes mellitus (average renin-high prorenin levels) and with hypertension only (average renin-average prorenin levels) had sPRR concentrations similar to healthy subjects. Renin-angiotensin system blockade was associated with increase of sPRR concentration by ≈12%. sPRR in patients with primary aldosteronism (low renin-low prorenin) and Gitelman syndrome (high renin-high prorenin) were similar and ≈10% higher than in healthy subjects. There was no correlation between sPRR and renin or prorenin. In conclusion, our results show that plasma sPRR concentrations are dependent on ethnicity and independent of renin, prorenin, and aldosterone concentrations in healthy subjects and in patients with contrasted degrees of renin-angiotensin system activity.
Assuntos
Aldosterona/sangue , Nefropatias Diabéticas/etnologia , Hipertensão Renal/etnologia , Receptores de Superfície Celular/sangue , Renina/sangue , ATPases Vacuolares Próton-Translocadoras/sangue , Adolescente , Adulto , Idoso , População Negra/estatística & dados numéricos , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/etnologia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/etnologia , Nefropatias Diabéticas/sangue , Feminino , Síndrome de Gitelman/sangue , Síndrome de Gitelman/etnologia , Humanos , Hiperaldosteronismo/sangue , Hiperaldosteronismo/etnologia , Hipertensão Renal/sangue , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Sistema Renina-Angiotensina/fisiologia , Solubilidade , População Branca/estatística & dados numéricos , Adulto JovemRESUMO
OBJECTIVES: Ambulatory blood pressure monitoring is the standard for determining patients at risk of hypertension. Left ventricular hypertrophy is common in kidney transplant recipients. We evaluated the correlation between blood pressure measures achieved by ambulatory blood pressure monitoring and conventional (office) methods. MATERIALS AND METHODS: This cross-sectional study was done from December 2009 to October 2010 at Alzahra Hospital in Isfahan, Iran. Sixty five participants, 35 kidney transplant recipients under 20 years old, and 30 control subjects of the same age were recruited. Five kidney recipients did not complete the study and were excluded. Blood pressure was measured by ambulatory blood pressure monitoring and conventional methods. Echocardiographic study was done for kidney transplant recipients. Serum brain natriuretic peptide and angiotensin II levels were determined in case and control groups. RESULTS: Office-recorded systolic and/or diastolic hypertension was observed in 43.4% and 55.3% of patients. According to ambulatory blood pressure monitoring, 86% of kidney transplant recipients had systolic BP load. Left ventricular hypertrophy (defined according to the left ventricular mass index [left ventricular mass index/height]) was seen in 53.3% of the patients. The existence of left ventricular hypertrophy revealed a positive correlation with ambulatory blood pressure monitoring systolic and diastolic night blood pressure and systolic nondipper. Left ventricular mass index showed a positive correlation with brain natriuretic peptide level. Furthermore, the existence of left ventricular hypertrophy was positively correlated with angiotensin II level. CONCLUSIONS: Only ambulatory blood pressure monitoring systolic and diastolic blood pressures (nondippers) were positively correlated with left ventricular hypertrophy and higher left ventricular mass index. Serum levels of brain natriuretic peptide and angiotensin II had a positive relation with left ventricular hypertrophy. Measuring brain natriuretic peptide and angiotensin II in the clinical setting screens patients at risk of left ventricular hypertrophy.
Assuntos
Angiotensina II/sangue , Ecocardiografia/estatística & dados numéricos , Hipertensão Renal/epidemiologia , Transplante de Rim/efeitos adversos , Peptídeo Natriurético Encefálico/sangue , Complicações Pós-Operatórias/epidemiologia , Adolescente , Biomarcadores/sangue , Pressão Sanguínea , Monitorização Ambulatorial da Pressão Arterial/estatística & dados numéricos , Criança , Pré-Escolar , Ritmo Circadiano , Estudos Transversais , Feminino , Humanos , Hipertensão Renal/sangue , Hipertensão Renal/diagnóstico por imagem , Hipertrofia Ventricular Esquerda/sangue , Hipertrofia Ventricular Esquerda/diagnóstico por imagem , Hipertrofia Ventricular Esquerda/epidemiologia , Masculino , Modelos Cardiovasculares , Complicações Pós-Operatórias/sangue , Complicações Pós-Operatórias/diagnóstico por imagem , Fatores de RiscoRESUMO
The study involved 53 patients with arterial hypertension in chronic kidney disease (chronic glomerulonephritis (CGN)). Lipid peroxidation was studied based on the content of diene conjugates and malondialdehyde. Protein peroxidation was studied based on the content of 2,4-dinitphenyl-aldogidrazons. The patients in all clinical variants of the CGN revealed increased activity of lipid peroxidation and the protein peroxidation, which is most pronounced in patients with nephrotic variant of CGN: increased levels of serum malondialdehyde medians occurred in 3.92 times and diene conjugates in 1.52 times (p<0.01). Increased activity of the oxidation of lipids and proteins has a negative impact on the organization of cell membranes of the renal structures and leads to loss of membrane barrier function.