Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0033687 (proteinuria)
 24,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study assessed whether the orally active endothelin-A- (ETA) receptor antagonist, BMS 182874 (BMS), affects systolic blood pressure (SBP), renal function and survival in salt-loaded stroke-prone spontaneously hypertensive rats (SHRSPs). Eight-week-old male and female SHRSPs were given a high-salt diet (4% NaCl) (n = 6/group). The treatment groups (n = 6/group), also on a high-salt diet, were administered BMS (40 mg/kg/day) which was mixed in the food. In untreated SHRSPs, mean survival was 136 days (range 96-194 days) in males, and 98 days (range 74-112 days) in females. Treatment with BMS increased survival to 223 days in males (range 129-280 days, p <0.01 vs controls) and 156 days (range 124-180, p < 0.05 vs controls) in females. SBP increased to approximately 240 mmHg in all groups. BMS had no effect on SBP in females and a small, but significant (p < 0.05), SBP-lowering effect in males. In control rats, severe renal disease was evident at 16 weeks (proteinuria, 161 +/- 1.3 mg/day). In the treated group, development of proteinuria was significantly delayed (13 +/- 0.5 mg/day at 16 weeks). In conclusion ETA-receptor antagonism prolongs survival and improves renal status, but has little effect on the progression of hypertension. These data suggest that interruption of the endothelin (ET) system by blockade of ETA-receptors may achieve protection from target-organ damage despite lack of a reduction in blood pressure.
J Cardiovasc Pharmacol 2000 Nov
PMID:Endothelin-A-receptor blockade improves renal function and doubles the lifespan of stroke-prone spontaneously hypertensive rats. 1107 4

Increased endothelin-1 (ET-1) levels were found in patients with chronic renal failure. These correlate with the severity of renal failure. Patients with elevated ET-1 concentrations show an increased cardiovascular mortality. The prevalence of severe left ventricular hypertrophy (LVH) is a very important factor for survival and morbidity in uremic patients The aim of this study was to assess the protective effect of ET-receptor antagonists in chronic uremia. Sprague Dawley rats were subtotally nephrectomized (SNX) and treated either with the endothelin-A- (ET(A)) receptor antagonist LU302146 or with the unselective ET(A)/ET(B)-receptor antagonist LU302872 (30 mg/kgbw/day both). After subtotal nephrectomy protein excretion SNX (130.0 +/- 22.5 mg/24 h) was increased in comparison to the ET(A)-group (446 +/- 103 mg/24 h) and the ET(AB)-group (23.2 +/- 37 mg/24 h) vs sham: 115 +/- 19 mg/24 h). Heart weight was decreased by the ET(A)/ET(B)-receptor antagonist LU302146. Left ventricular contractility was impaired in SNX by about 40%. Treatment with the ET-receptor antagonists prevented the impairment in left ventricular function. Our study results provide a possible therapeutic approach using ET receptor antagonists to reduce cardiac hypertrophy and renal proteinuria. Further human studies are needed to show whether this protection of the heart and kidney might influence the survival and life-expectancy of patients suffering from chronic renal failure.
J Cardiovasc Pharmacol 2000 Nov
PMID:Endothelin-receptor antagonists in uremic cardiomyopathy. 1107 17

The blood-pressure lowering activity, tolerability, and safety of irbesartan was evaluated in 52 hypertensive patients with chronic renal insufficiency. After a 3-week placebo period, once-daily irbesartan was administered for 12 weeks at a daily dose of 150 mg titrated to 300 mg. A second, non-angiotensin-converting enzyme inhibitor, antihypertensive drug was added after 8 weeks as needed. Twenty-four-hour creatinine clearance was determined and renal clearance studies of inulin and para-aminohippurate were done in a subset of 11 patients. Trough sitting blood pressures were reduced at the end of the first week in all groups. At weeks 4, 8, and 12 the reductions in systolic blood pressure/diastolic blood pressure averaged -11.9/-8.7, -10.8/-9.4, and -14.7/-12.1 mm Hg in patients with mild renal insufficiency and -7.7/-6.3, -13.1/-11.8, and -14.1/-10.6 mm Hg in patients with moderate-to-severe renal insufficiency. Creatinine clearance, glomerular filtration rate, and effective renal plasma flow were stable. Irbesartan was withdrawn in only five patients because of adverse clinical or laboratory experience. Hyperkalemia (>6 mEq/l) requiring discontinuation of irbesartan occurred in only one patient. Once-daily irbesartan given as monotherapy at dose of 150-300 mg or in combination with other antihypertensive drugs is effective in reducing blood pressure in hypertensive patients with chronic renal disease. Irbesartan regimens are well tolerated in all groups. In addition, the blood pressure-lowering effect of irbesartan is accompanied by a significant reduction in proteinuria in patients with chronic renal insufficiency.
J Cardiovasc Pharmacol 2001 Sep
PMID:Irbesartan effects on renal function in patients with renal impairment and hypertension: a drug-withdrawal study. 1148 53

Atherosclerosis and coronary artery disease (CAD) are now the commonest sequelae of hypertension and all clinical manifestations of CAD occur in excess in persons with elevated blood pressure. Risk increases in relation to the extent of blood pressure elevation whether this is in the systolic or diastolic component, at any age and in either sex. Even isolated systolic hypertension increases cardiovascular risk. Elevated pressures are often accompanied by lipid abnormalities, hyperglycemia, elevated fibrinogen, obesity, and ECG abnormalities, all of which augment the risk. These risk factors associated with hypertension influence the coronary risk potential more than the nature of the blood pressure elevation. Although blood pressure makes an independent contribution to CAD, the risk at any level of pressure is markedly influenced by the cardiovascular risk profile. In mild to moderate hypertension in particular, the risk of CHD is concentrated in those who have impaired glucose tolerance, increased total/HDL ratio, ECG abnormalities, and smoke cigarettes. One or more of these associated risk factors also predisposes to other cardiovascular sequelae of hypertension, including stroke, peripheral vascular disease, and cardiac failure. The presence of organ involvement indicated by proteinuria, evidence of impaired ventricular function, or left ventricular hypertrophy greatly escalates the risk and usually indicates a compromised coronary circulation. Most myocardial infarctions and sudden deaths occur prior to the appearance of such evidence. Hypertensive risk assessment requires consideration of the multivariate risk profile because of the interdependence of the risk factors. The nature and urgency of treatment is better determined from such a risk profile than from the blood pressure parameters alone. Optimal preventive management of hypertension requires more than normalization of the blood pressure if coronary sequelae are to be avoided.
J Cardiovasc Pharmacol 1990
PMID:Influence of multiple risk factors on the hazard of hypertension. 1152 37

The goal of treatment of hypertension in older persons is to lower the blood pressure to <140/90 mm Hg. Older persons with diastolic hypertension should have their diastolic blood pressure lowered to 80 to 85 mm Hg. The blood pressure should be lowered to 130/85 mm Hg in persons with diabetes mellitus or renal insufficiency and to 125/75 mm Hg in persons with proteinuria of 1 gram per 24 hours. Diuretics or beta blockers should be used as initial drugs in the treatment of hypertension. The choice of antihypertensive drug in older persons with associated medical conditions depends on the associated medical conditions.
Cardiovasc Drugs Ther 2001
PMID:Commentary on treatment of hypertension in the elderly. 1171 97

T-type Ca(2+) channels have properties different from those of the L-type and are involved in cardiac pacemaking and regulation of blood flow, but not in myocardial contraction. Efonidipine is an antihypertensive and antianginal drug with dihydropyridine structure that was recently found to block both L- and T-type Ca(2+) channels. In isolated myocardial and vascular preparations, efonidipine has potent negative chronotropic and vasodilator effects but only a weak negative inotropic effect. In experimental animals and patients, reduction of blood pressure by the drug was accompanied by no or minimum reflex tachycardia leading to improvement of myocardial oxygen balance and maintenance of cardiac output. Efonidipine increased glomerular filtration rate without increasing intraglomerular pressure. By relaxing both the afferent and efferent arterioles, efonidipine markedly reduced proteinuria. Thus, efonidipine, an L- and T-type dual Ca(2+) channel blocker, appears to have an ideal profile as an antihypertensive and antianginal drug with organ-protective effects in the heart and kidney.
Cardiovasc Drug Rev 2002
PMID:Efonidipine hydrochloride: a dual blocker of L- and T-type ca(2+) channels. 1207 May 36

Microalbuminuria (MA) i.e. slightly elevated albumin excretion in the urine, is now considered to be an atherosclerotic risk factor. MA predicts future cardiovascular disease risk in diabetic patients, in elderly patients, as well as in the general population. It has been implicated as an independent risk factor for cardiovascular disease and premature cardiovascular mortality for patients with type 1 and type 2 diabetes mellitus, as well as for patients with essential hypertension. Although microalbuminuria is associated with a certain degree of sub-clinical artherosclerotic damage, it is not known how early in the atherosclerotic process microalbuminuria appears. Epidemiological studies have shown an association between MA and insulin resistance, obesity, salt sensitivity and dyslipidaemia in patients with essential hypertension and diabetes. Patients with microalbuminuria are also characterised by an increased prevalence of left ventricular hypertrophy and retinal microvascular lesions. Microalbuminuria, is associated with an excess of other cardiovascular risk factors. The mechanisms linking microalbuminuria and risk for cardiovascular disease are not fully understood, but in subjects at risk it may be related to increased transvascular leakiness of albumin in systemic as well as renal vessels. A recent concept is that microalbuminuria is a marker of extensive endothelial dysfunction or generalised vasculopathy, which may lead to heightened atherogenic states. One possible explanation is that endothelial dysfunction might promote increased penetration of atherogenic lipoprotein particles in the arterial wall, but glycaemic status, insulin resistance, procoagulant state and adhesion molecules have all been implicated in the pathogenesis. Current evidence suggests that tight blood pressure control may reduce the risk of microalbuminuria in diabetic patients with hypertension and that inhibitors of the rennin-angiotensin system (RAS) can prevent or delay the progression of microalbuminuria to overt nephropathy in normotensive persons. ACE inhibitors are currently recognised as first-line antihypertensive therapy in diabetic patients with proteinuria, and these agents afford unique benefits in modifying the progression and severity of cardiovascular disease (CVD) as well as of diabetic nephropathy. Whether albuminuria is a risk factor or just a marker for CV disease, it identifies the high-risk diabetic patient who should be targeted for early, aggressive intervention against proven risk factors. If persistent microalbuminuria is confirmed, strict blood pressure control with added RAS inhibition should be pursued in an attempt to stabilise or even reduce microalbuminuria, preserve kidney function and possibly improve cardiovascular risk.
Cardiovasc J S Afr
PMID:The link between microalbuminuria, endothelial dysfunction and cardiovascular disease in diabetes. 1238 63

The present experiments were designed to assess the renal functional response to alterations in nitric oxide formation in animals with different forms of nephropathy. To address this issue, the effects of Nomega-nitro-L-arginine methyl ester (L-NAME) or L-arginine were assessed in animal models exhibiting arterial hypertension due to chronic nitric oxide inhibition (L-NAME, 50 mg/l in drinking water for 12 weeks) or diabetes mellitus (streptozotocin, 60 mg/kg IP). Vehicle-treated, age-matched animals served as controls. Following 12 weeks of pretreatment, mean arterial pressure (MAP), renal hemodynamics, urinary albumin, and electrolyte excretion were determined in standard clearance experiments prior to and following infusion of L-NAME (50 microg/kg/min), l-arginine (5 mg/kg/min), or saline vehicle. In control animals, L-NAME resulted in an increase in MAP and renal vascular resistance and a decline in glomerular filtration rate and renal plasma flow, as expected. L-arginine had no effect on renal hemodynamics. In nitric oxide-depleted hypertensive animals, L-NAME had no additional effect on MAP or renal hemodynamics. Infusion of L-arginine reduced elevated MAP but did not reverse changes in renal hemodynamics. Diabetic rats demonstrated glomerular hyperfiltration and proteinuria. No significant changes in MAP or renal hemodynamics were observed following infusion of L-NAME or L-arginine, respectively. However, L-NAME increased urinary albumin excretion in the absence of hemodynamic changes. The effects of nitric oxide on vascular tone were shown to be dependent on the vascular bed and the underlying disease. Variations in local nitric oxide formation and susceptibility may account for the differential response of the systemic and renal vasculature and contribute to the degree of renal functional impairment observed in different systemic diseases.
J Cardiovasc Pharmacol 2002 Nov
PMID:Differential renal response to Nomega-nitro-L-arginine methyl ester and L-arginine in rats with hypertensive or diabetic nephropathy. 1240 87

Combination of nonhypotensive doses of valsartan and enalapril markedly improved survival (+87%) compared with untreated animals (37%) in spontaneously hypertensive rats (SHRs) with endothelial dysfunction. However, the combination had no effect on kidney function, and proteinuria persisted over the 12 weeks of the study. It was hypothesized that the greater survival was due to improvement in endothelial function or coronary vasculature despite blockade of nitric oxide synthase and high blood pressure. Therefore, endothelial function was evaluated in isolated aortic ring and maximal coronary blood flow was studied in isolated perfused SHR hearts (20-24 weeks) treated with -nitro-l-arginine methyl ester (L-NAME) (50 mg/l) for 4 weeks. The animals received vehicle, valsartan 5 mg/kg/d, enalapril 1 mg/kg/d, valsartan 50 mg/kg/d, or the combination valsartan 5 mg/kg/d with enalapril 1 mg/kg/d in drinking water. Normotensive Wistar-Kyoto (WKY) rats were used as control. Blood pressure was measured by telemetry. Histopathology was performed on heart, kidney (hematoxylin-eosin), and aorta (Masson trichrome). L-NAME elevated blood pressure by 50 mm Hg after vehicle (199 +/- 5 mm Hg). Valsartan 50 mg/kg/d completely abolished this increase (150 +/- 4 mm Hg) whereas the valsartan-enalapril combination synergistically decreased blood pressure (-37 mm Hg at 162 +/- 7 mm Hg) compared with monotherapy (valsartan 5 mg/kg/d -10 mm Hg; enalapril 1 mg/kg/d -15 mm Hg). All treatments improved the histopathology, most markedly in those receiving the valsartan-enalapril combination. The severity mean grades for lesions were 2.1, 1.9, 1.7, 1.1, and 0.9 in vehicle-treated SHRs, enalapril 1 mg/kg/d, valsartan 5 mg/kg/d, valsartan 5 or 50 mg/kg/d, and the valsartan-enalapril combination, respectively, compared with 0.02 in WKY rats. Acetylcholine-induced relaxation was significantly greater in treated SHRs than after vehicle (-40% at 0.1 mmol acetylcholine) but the combination induced the maximal relaxation (-85%). The ratio of maximal tension induced by serotonin in rings with and without endothelium was 1.4 and 1.3 in vehicle and valsartan 5 mg/kg/d-treated rats whereas it did not differ from 1 in WKY rats and all other treated groups. The cardiac hypertrophy (+27%) was prevented by valsartan 50 mg/kg/d and the valsartan-enalapril combination. Coronary reserve was significantly increased by valsartan 50 mg/kg/d (+85% at 7.8 +/- 0.7 ml/min/g) and the valsartan-enalapril combination (+42% at 6.0 +/- 0.4 ml/min/g) compared with 4.2 +/- 0.5 (vehicle). This was not different of 8.8 +/- 0.5 (WKYs). Despite the maintenance of a high blood pressure, low-dose valsartan-enalapril significantly improved endothelial function and histopathology and increased coronary reserve in SHRs chronically receiving L-NAME.
J Cardiovasc Pharmacol 2002 Nov
PMID:Combination of low-dose valsartan and enalapril improves endothelial dysfunction and coronary reserve in Nomega-nitro-L-arginine methyl ester-treated spontaneously hypertensive rats. 1240 88

The authors recently observed an age-dependent reduction in the diuretic and natriuretic responses to plasma volume expansion in uninephrectomized control and glucose-intolerant rats. To determine the involvement of angiotensin II AT receptors in this phenomenon, the authors tested the hypothesis that chronic candesartan treatment preserves renal excretory function in the uninephrectomized rat. Control and glucose-intolerant rats underwent right nephrectomy at 4 weeks of age. Two weeks later, the animals in each group were further subdivided and maintained on tap water containing either candesartan cilexetil (10 mg. kg(-1). day(-1) ) or vehicle. Renal excretory responses to acute extracellular fluid volume expansion (5% of body weight over 30 min) were determined in the 9-month-old conscious animal. Candesartan treatment markedly reduced the mean arterial pressure of controls and glucose-intolerant rats. Nonetheless, the baseline rates of fluid and electrolyte excretion, as well as the saline volume-induced diuretic, natriuretic, and kaliuretic responses, were greater in the candesartan-treated rats than in their vehicle-treated counterparts. The augmented baseline rates of fluid and sodium excretion in candesartan-treated rats were caused by a reduction in tubular reabsorption activity and an increase in glomerular filtration rate. However, the candesartan-mediated enhancement in saline volume-induced diuresis and natriuresis was caused by a reduction in tubular reabsorption activity. In addition to improving renal function, candesartan treatment reduced proteinuria in both groups. In conclusion, chronic blockade of the angiotensin II receptors exerts hypotensive and renoprotective effects in the aging uninephrectomized rat.
J Cardiovasc Pharmacol 2003 Jan
PMID:Renoprotective effects of chronic candesartan treatment in uninephrectomized rat. 1250 25


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>