Assuntos
Humanos , Masculino , Feminino , Antagonistas Adrenérgicos beta/uso terapêutico , Hipertensão Renal/prevenção & controle , Falência Renal Crônica/prevenção & controle , Anti-Hipertensivos/uso terapêutico , Fatores de Risco , Diálise Renal , Progressão da Doença , Relação Dose-Resposta a Droga , Hipertensão Renal/etiologia , Falência Renal Crônica/terapia , Falência Renal Crônica/epidemiologiaRESUMO
Decreasing sodium intake has been associated with improvements in blood pressure (BP) and proteinuria, two important risk factors for CVD and chronic kidney disease (CKD) progression. We aimed to investigate the role of sodium intake by examining the effect of changes in sodium intake over 1 year on BP and proteinuria in people with early stage CKD. From thirty-two general practices, 1607 patients with previous estimated glomerular filtration rate of 59-30 ml/min per 1.73 m² and mean age of 72.9 (sd 9.0) years were recruited. Clinical assessment, urine and serum biochemistry testing were performed at baseline and after 1 year. Sodium intake was estimated from early morning urine specimens using an equation validated for this study population. We found that compared with people who increased their sodium intake from ≤ 100 to >100 mmol/d over 1 year, people who decreased their intake from >100 to ≤ 100 mmol/d evidenced a greater decrease in all BP variables (Δmean arterial pressure (ΔMAP) = -7.44 (SD 10.1) v. -0.23 (SD 10.4) mmHg; P<0.001) as well as in pulse wave velocity (ΔPWV = -0.47 (SD 1.3) v. 0.08 (SD 1.88) m/s; P<0.05). Albuminuria improved only in albuminuric patients who decreased their sodium intake. BP improved in people who maintained low sodium intake at both times and in those with persistent high intake, but the number of anti-hypertensive increased only in the higher sodium intake group, and PWV improved only in participants with lower sodium intake. Decreasing sodium intake was an independent determinant of ΔMAP. Although more evidence is needed, our results support the benefits of reducing and maintaining sodium intake below 100 mmol/d (2.3-2.4 g/d) in people with early stages of CKD.
Assuntos
Dieta Hipossódica , Hipertensão Renal/prevenção & controle , Cooperação do Paciente , Insuficiência Renal Crônica/dietoterapia , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Terapia Combinada , Progressão da Doença , Inglaterra/epidemiologia , Feminino , Seguimentos , Humanos , Hipertensão Renal/epidemiologia , Hipertensão Renal/etiologia , Perda de Seguimento , Masculino , Pessoa de Meia-Idade , Pacientes Desistentes do Tratamento , Atenção Primária à Saúde , Estudos Prospectivos , Insuficiência Renal Crônica/fisiopatologia , Insuficiência Renal Crônica/terapia , Insuficiência Renal Crônica/urina , Fatores de Risco , Índice de Gravidade de Doença , Sódio/urinaRESUMO
Cecropia glaziovii Sneth is a common tree at the Southeastern Brazilian coast. As many other species of the genus, it shares the reputed folk use to treat heart failure, cough, asthma and bronchitis. The plant has been cultivated under controlled conditions and the 2% aqueous extract (AE) prepared with the dried leaves was standardized by its chemical contents on catechins, flavonoids and procyanidins. The present paper reports the antihypertensive activity of AE and of n-butanol fraction (BuF), an enriched semi-purified butanolic fraction used to isolate the main chemical constituents. Oral administration of AE and BuF induced hypotension in normotensive rats. The effect of AE (0.5 g/kg/bi, p.o.) was time and dose-dependent peaking at 2-3 weeks after daily administration. BuF was faster but not more active than AE. Both extracts decreased the hypertension of spontaneous hypertensive rats, the hypertension induced in rats by L-NAME treatment and that induced by constriction of one renal artery. The antihypertensive effect was maintained for as long as 60 days of treatment and was reversible upon drug washout at the same rate of its establishment. Acute i.v. administration of BuF to anesthetized rats induced a fast short-lasting hypotension and inhibited the pressor responses to noradrenaline, angiotensin I and angiotensin II by 40%. These results were indirect indications that the hypotension induced by AE is not related to ACE inhibition, increased NO synthesis, or specific blockade of alpha1 and AT1 receptors. It can be suggested that BuF interferes with the calcium handling mechanisms in smooth muscle cells and neurons. Intravenous injection of five out of nine compounds isolated from BuF produced immediate but short-lasting hypotension that does not correlate with the onset of the hypotension after oral treatment. This finding suggests that they may not be the compounds directly responsible for the delayed and sustained hypotension after per os administration of AE. The many compounds isolated from AE are under evaluation to determine its pharmacokinetics, mechanisms of action and interactions necessary to yield the plant effect. Although its mechanism is still unknown, AE seems to be an effective and safe antihypertensive phytomedicine.
Assuntos
Anti-Hipertensivos/farmacologia , Fitoterapia , Extratos Vegetais/farmacologia , Urticaceae , Administração Oral , Animais , Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/química , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Relação Dose-Resposta a Droga , Hipertensão/prevenção & controle , Hipertensão Renal/prevenção & controle , Injeções Intravenosas , Masculino , Camundongos , Extratos Vegetais/administração & dosagem , Extratos Vegetais/química , Extratos Vegetais/uso terapêutico , Folhas de Planta , Ratos , Ratos WistarRESUMO
BACKGROUND: Cellophane wrapping of the kidneys (Page kidney) induces perinephrits and hypertension, assumed to be due to renal ischemia resulting from parenchymal compression by the fibrous hull surrounding the kidneys. We investigated if interstitial nephritis, rather than plasma angiotensin activity, played a role in the development of hypertension in the Page kidney model. METHODS: We followed for 7 weeks rats with bilateral cellophane wrapping of the kidneys that received 20 mg/kg/day of the immunosuppressive antiproliferative drug mycophenolate mofetil (MMF) (two-kidney wrap/MMF) (N = 10) or vehicle (two-kidney wrap) (N = 10), and sham-operated rats (N = 10). RESULTS: The two-kidney wrap group had progressive increment in blood pressure, inflammatory damage occupying 25% to 50% of the renal tubulointerstitial region and increased number of angiotensin II-positive cells, angiotensin II content, and oxidative stress in the kidney. MMF treatment prevented the development of hypertension and renal inflammation without modifying the perinephritic hull or the increment it induced in the intrarenal pressure. The plasma levels of angiotensin II were similar in the two-kidney wrap group, the two-kidney wrap/MMF group and the sham-operated animals and unchanged from baseline, despite the blood pressure increase in the two-kidney wrap group. CONCLUSION: Our results indicate that renal wrap hypertension is unrelated to plasma angiotensin II levels and related to the inflammatory damage caused by the external compression of the kidney.
Assuntos
Hipertensão Renal/etiologia , Isquemia/complicações , Nefrite Intersticial/complicações , Angiotensina II/sangue , Animais , Pressão Sanguínea , Peso Corporal , Celofane , Modelos Animais de Doenças , Glutationa/metabolismo , Hipertensão Renal/patologia , Hipertensão Renal/prevenção & controle , Imunossupressores/farmacologia , Isquemia/tratamento farmacológico , Isquemia/patologia , Rim/metabolismo , Rim/patologia , Testes de Função Renal , Masculino , Malondialdeído/metabolismo , Ácido Micofenólico/análogos & derivados , Ácido Micofenólico/farmacologia , Nefrite Intersticial/tratamento farmacológico , Nefrite Intersticial/patologia , Pressão , Ratos , Ratos Sprague-DawleyRESUMO
BACKGROUND: Interstitial mononuclear cell infiltration is a feature of experimental models of salt-sensitive hypertension (SSHTN). Since several products of these cells are capable of modifying local vascular reactivity and sodium reabsorption, we investigated whether mycophenolate mofetil (MMF), a drug known to inhibit infiltration and proliferation of immune cells, would modify the SSHTN induced by angiotensin II (Ang II) infusion. METHODS: Sprague-Dawley rats received Ang II for two weeks using subcutaneous minipumps. A high-sodium (4% NaCl) diet was started on the third week and was maintained until the eighth week. MMF (30 mg/kg, N = 15), an immunosuppressive drug, or vehicle (N = 15) was given daily by gastric gavage during the initial three weeks. Sham-operated rats (N = 9) were used as controls. Body weight, blood pressure (tail-cuff plethysmography), and serum creatinine were determined weekly. Urinary malondialdehyde (MDA) excretion, renal histology, and immunohistology, including the presence of Ang II and superoxide-producing cells, were analyzed at the end of Ang II infusion and at eight weeks. RESULTS: MMF treatment did not modify hypertension induced during exogenous Ang II infusion, but prevented the subsequent SSHTN. Tubulointerstitial injury resulting from Ang II infusion was significantly reduced by MMF treatment, as were proliferative activity, T-cell infiltration and activation (interleukin-2 receptor expression), superoxide-producing cells, and urinary MDA excretion. Ang II-producing cells were present in the renal tubulointerstitium of rats with SSHTN (60 +/- 30 Ang II-positive cells/mm(2) at 8 weeks) and were reduced by two thirds in the MMF-treated group. Forty percent of lymphocytes infiltrating the tubulointerstitium stained positive for Ang II. The expression of Ang II receptors in the kidney was unmodified. CONCLUSIONS: SSHTN resulting from Ang II infusion is associated with infiltration and activation of immune cells that produce Ang II. MMF treatment reduces these features and prevents the development of SSHTN.
Assuntos
Angiotensina II/farmacologia , Anti-Inflamatórios não Esteroides/farmacologia , Hipertensão Renal/tratamento farmacológico , Ácido Micofenólico/farmacologia , Vasoconstritores/farmacologia , Angiotensina II/análise , Animais , Pressão Sanguínea/efeitos dos fármacos , Peso Corporal , Divisão Celular/fisiologia , Creatinina/sangue , Modelos Animais de Doenças , Fibronectinas/análise , Hipertensão Renal/induzido quimicamente , Hipertensão Renal/prevenção & controle , Rim/química , Rim/imunologia , Rim/patologia , Leucócitos Mononucleares/imunologia , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Malondialdeído/urina , Ácido Micofenólico/análogos & derivados , Osteopontina , Ratos , Ratos Sprague-Dawley , Receptor Tipo 1 de Angiotensina , Receptor Tipo 2 de Angiotensina , Receptores de Angiotensina/análise , Sialoglicoproteínas/análise , Superóxidos/metabolismo , Vasoconstritores/análiseRESUMO
The effects of chronic intracerebroventricular (i.c.v.) injections of the alpha2-adrenoceptor agonist, xylazine, on blood pressure were examined in DOCA-salt rats. Acute studies also examined the renal sympathetic nerve activity (RSNA) and renal excretory responses produced by i.c.v. xylazine in rats with established DOCA-salt hypertension. Rats implanted with a chronic i.c.v. cannula for drug injection were used. In chronic studies, four groups were investigated: control rats treated with s.c. soybean oil and i.c.v. saline; DOCA-salt rats (s.c. deoxycorticosterone acetate) receiving i.c.v. saline, xylazine or the alpha2-adrenoceptor antagonist, yohimbine. During vehicle or DOCA-salt treatment, xylazine (0.2 ng/microg) or yohimbine (10O microg/kg) was injected i.c.v. daily (three times). In DOCA-salt rats receiving i.c.v. saline, resting mean arterial pressure (MAP) was elevated on days 15 and 30 (135 +/- 5 and 160 +/- 6 mmHg, respectively). Chronic i.c.v. xylazine significantly attenuated the rise in MAP produced by DOCA-salt (day 15, 118 +/- 5 mmHg; day 30, 121 +/- 4 mmHg). Alternatively, chronic i.c.v. yohimbine shortened the onset (day 15, 152 +/- 7 mmHg) and augmented the hypertension in DOCA-salt rats (0 survival by day 30). In acute studies, i.c.v. xylazine elicited a profound natriuresis and diuresis as well as a reduction in RSNA without altering MAP. This study demonstrates that the ongoing (tonic) activity of central alpha2-adrenoceptor mechanisms are critically involved in regulating blood pressure in the DOCA-salt treated rat. In this manner, an enhanced activity of central alpha2-adrenoceptor systems acts to protect against a rise in blood pressure. In contrast, the attenuation of central alpha2-adrenoceptor stimulation evokes hypertension. The central action of xylazine to prevent hypertension may be associated with the inhibition of sympathetic outflow to the kidneys and evokes an enhanced natriuresis. By inhibiting the avid sodium retention elicited by DOCA-salt treatment, the central activation of alpha2-adrenoceptors delays the onset and the severity of hypertension in this pathological model.
Assuntos
Desoxicorticosterona/farmacologia , Hipertensão Renal/metabolismo , Hipertensão Renal/prevenção & controle , Receptores Adrenérgicos alfa 2/metabolismo , Sódio na Dieta/farmacologia , Agonistas alfa-Adrenérgicos/farmacologia , Antagonistas Adrenérgicos alfa/farmacologia , Animais , Pressão Sanguínea/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Hipertensão Renal/induzido quimicamente , Injeções Intraventriculares , Rim/inervação , Rim/fisiologia , Rim/cirurgia , Masculino , Nefrectomia , Ratos , Ratos Wistar , Sódio na Dieta/urina , Sistema Nervoso Simpático/efeitos dos fármacos , Sistema Nervoso Simpático/fisiologia , Xilazina/farmacologia , Ioimbina/farmacologiaRESUMO
Radiation of the kidney often leads to renal failure. The contribution of arterial hypertension to the development of this complication is unclear. The aim of this study was to determine the renal effects of antihypertensive therapy in 1- and 2-kidney rat models of radiation nephritis. Five groups of Long Evans rats had X-irradiation of the left kidney. In groups 1 and 2, the right kidney was left undisturbed (2-kidney model). The rats in group 3, 4 and 5 underwent right nephrectomy 21 days before radiation (1-kidney model). Groups 1 and 3 received no drug treatment and served as controls for each model. Groups 2 and 4 had enalapril 50 mg/l in drinking water and group 5 hydrochlorothiazide (HCT) 200 mg/l, also in drinking water. Blood pressure increased significantly in both control groups and remained normal throughout the study in all treated groups. At the end of the study, mean urinary protein excretion was lower in the two enalapril-treated groups but not in HCT-treated animals. Groups 1 and 2 (2-kidney models) showed similar increments in plasma creatinine (PCreat), and, in both groups, the creatinine clearance (CCreat) dropped to the same extent. Among nephrectomized animals (1-kidney model), PCreat was lower and CCreat higher in the enalapril-treated group. Consistent with these findings, glomerular sclerosis was less severe in both enalapril-treated groups. We conclude that, in radiation nephritis, lowering blood pressure with enalapril exerts a beneficial effect on renal function and structure, whereas a similar reduction in blood pressure induced by HCT does not.
Assuntos
Enalapril/farmacologia , Hidroclorotiazida/farmacologia , Nefrite/tratamento farmacológico , Lesões Experimentais por Radiação/tratamento farmacológico , Animais , Pressão Sanguínea/efeitos dos fármacos , Hipertensão Renal/prevenção & controle , Nefrectomia , Nefrite/patologia , Nefrite/fisiopatologia , Lesões Experimentais por Radiação/patologia , Lesões Experimentais por Radiação/fisiopatologia , Ratos , Fatores de TempoRESUMO
1. The effects of chronically administered cicletanine (CICL), an antihypertensive and prostacyclin stimulating agent, on glomerular hemodynamics were evaluated after 30 (CRF-30) or 60 (CRF-60) days of chronic renal failure (CRF) induced by 5/6 nephrectomy in Munich-Wistar rats. 2. CICL administration (3 mg kg-1 day-1, N = 5) for 60 days did not modify glomerular hemodynamics of normal rats (control group). The CRF-60 group (N = 6) presented a significant increase in mean arterial pressure (MAP) compared with control (122 +/- 7 vs 98 +/- 2 mmHg, P < 0.05), which was attenuated by CICL (113 +/- 7 vs 122 +/- 7 mmHg). 3. Hyperfiltration and hyperperfusion were observed in both CRF groups after 30 (N = 5) but not after 60 days of CRF, 73.9 +/- 6.3 and 48.2 +/- 3.2 vs 36.8 +/- 2.6 nl/min for SNGFR and 200 +/- 17 and 147 +/- 8 vs 112 +/- 8 nl/min for QA in CRF-30, CRF-60 vs control group, respectively. However, glomerular hypertension was demonstrable for both CRF groups only after 60 days. CICL treatment starting 7 days prior to nephrectomy reduced the transcapillary hydraulic pressure difference (delta P) in both groups, 36 +/- 3 vs 30 +/- 2 mmHg (30 days) and 41 +/- 4 vs 34 +/- 2 (60 days), but did not significantly modify arteriolar resistances or glomerular hemodynamics, suggesting that the reduction in MAP in response to CICL may have been responsible for the decrease in delta P. CICL administration did not prevent the proteinuria or glomerular sclerosis associated with CRF. 4. The results suggest that the administration of CICL for 30 (N = 4) to 60 days (N = 7) was sufficient to prevent systemic hypertension associated with CRF but not to reduce the additional glomerular hemodynamic factors that participate in the progression of CRF.
Assuntos
Hipertensão/prevenção & controle , Falência Renal Crônica/fisiopatologia , Glomérulos Renais/efeitos dos fármacos , Piridinas/farmacologia , Animais , Glomerulosclerose Segmentar e Focal/prevenção & controle , Hipertensão/etiologia , Hipertensão Renal/prevenção & controle , Falência Renal Crônica/complicações , Glomérulos Renais/fisiopatologia , Proteinúria/prevenção & controle , Piridinas/uso terapêutico , Ratos , Ratos Wistar , Fatores de TempoRESUMO
1. The effects of chronically administered cicletanine (CICL), an antihypertensive and prostacyclin stimulating agent, on glomerular hemodynamics were evaluated after 30 (CRF-30) or 60 (CRF-60) days of chronic renal failure (CRF) induced by 5/6 nephrectomy in Munich-Wistar rats. 2. CICL administration (3 mg kg-1 day-1, N = 5) for 60 days did not modify glomerular hemodynamics of normal rats (control group). The CRF-60 group (N = 6) presented a significant increase in mean arterial pressure (MAP) compared with control (122 +/- 7 vs 98 +/- 2 mmHg, P < 0.05), which was attenuated by CICL (113 +/- 7 vs 122 +/- 7 mmHg). 3. Hyperfiltration and hyperperfusion were observed in both CRF groups after 30 (N = 5) but not after 60 days of CRF, 73.9 +/- 6.3 and 48.2 +/- 3.2 vs 36.8 +/- 2.6 nl/min for SNGFR and 200 +/- 17 and 147 +/- 8 vs 112 +/- 8 nl/min for QA in CRF-30, CRF-60 vs control group, respectively. However, glomerular hypertension was demonstrable for both CRF groups only after 60 days. CICL treatment starting 7 days prior to nephrectomy reduced the transcapillary hydraulic pressure difference (delta P) in both groups, 36 +/- 3 vs 30 +/- 2 mmHg (30 days) and 41 +/- 4 vs 34 +/- 2 (60 days), but did not significantly modify arteriolar resistances or glomerular hemodynamics, suggesting that the reduction in MAP in response to CICL may have been responsible for the decrease in delta P. CICL administration did not prevent the proteinuria or glomerular sclerosis associated with CRF. 4. The results suggest that the administration of CICL for 30 (N = 4) to 60 days (N = 7) was sufficient to prevent systemic hypertension associated with CRF but not to reduce the additional glomerular hemodynamic factors that participate in the progression of CRF
Assuntos
Animais , Ratos , Glomérulos Renais , Hipertensão/prevenção & controle , Insuficiência Renal Crônica/fisiopatologia , Piridinas/farmacologia , Glomérulos Renais/fisiopatologia , Glomerulosclerose Segmentar e Focal/prevenção & controle , Hipertensão Renal/prevenção & controle , Hipertensão/etiologia , Insuficiência Renal Crônica/complicações , Proteinúria/prevenção & controle , Piridinas/uso terapêutico , Ratos Wistar , Fatores de TempoAssuntos
Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Hipertensão Renal/prevenção & controle , Isradipino/uso terapêutico , Falência Renal Crônica/prevenção & controle , Angiotensina II/metabolismo , Animais , Pressão Sanguínea/efeitos dos fármacos , Humanos , Hipertensão Renal/complicações , Hipertensão Renal/fisiopatologia , Falência Renal Crônica/etiologia , Glomérulos Renais/fisiopatologia , RatosAssuntos
Humanos , Animais , Ratos , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Hipertensão Renal/prevenção & controle , Insuficiência Renal Crônica/prevenção & controle , Angiotensina II/metabolismo , Glomérulos Renais/fisiopatologia , Hipertensão Renal/complicações , Hipertensão Renal/fisiopatologia , Insuficiência Renal Crônica/etiologia , Pressão ArterialRESUMO
We analyzed studies concerned with four important aspects of vesicoureteral reflux in infancy and childhood: the imaging procedures for the evaluation of vesicoureteral reflux, the treatment of reflux, and the correlation between reflux and later development of hypertension and end-stage kidney disease. The objectives of the study were to evaluate the validity and reliability of the current literature, to draw conclusions, and to recommend future studies for unresolved issues. We reached the following conclusions: (1) Retrograde cystography should be the gold standard for diagnosing vesicoureteral reflux. When ultrasonography and cystography are performed together, all clinically important abnormalities in the urinary system are detected. Intravenous pyelography is needed only when either or both of these studies are abnormal. (2) Other than abolishing reflux, surgery offers no short-term advantages (in terms of preventing breakthrough urinary tract infections, improving renal function, or preventing the development of new scars, hypertension, or end-stage kidney disease) over medical management. (3) The short periods of follow-up and methodologic flaws encountered in the reviewed studies make determination of the incidence of hypertension in children with vesicoureteral reflux impossible. (4) Although indications for an association between vesicoureteral reflux and end-stage kidney disease exist, the strength of this association has not been determined.