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

To investigate the role of endothelin (ET) in severe hypertension, endothelial dysfunction hypercholesterolemic stroke-prone spontaneously hypertensive rats (SHRSP on a 5% cholesterol diet) were additionally fed with 1% NaCl and 0.023% nitro-L-arginine. Under these conditions, all untreated rats died within 30 days (median 17 days). A significant prolongation of survival (median 33 days) was achieved by combination treatment with hydralazine and the ETA receptor antagonist LU 135252. Monotherapy was less effective (LU 135252 18 days; hydralazine 28 days). Likewise, only treatment with the combination completely prevented the increase in systolic arterial pressure (SAP) seen in the control group during the first 10 days and delayed development of hypertension during the subsequent observation period. The superior efficacy of the combination was also reflected by improved kidney function. After 20 days of treatment, proteinuria had only increased to 1,272 +/- 135 mg/kg/day, a reduction of 45% compared to the untreated control group (2,300 +/- 346 mg/kg/day; p < 0.05). In this animal model of aggravated hypertension and endothelial dysfunction, the combination of LU 135252 with hydralazine was superior compared to either monotherapy. Therefore, the combination of an ETA receptor antagonist with vasodilators may be a potent therapy to improve blood pressure, renal function, and survival in severe hypertension with concomitant metabolic disease.
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PMID:Endothelin-A receptor antagonist combined with hydralazine improves survival and renal function in hypertensive rats. 959 50

Essential hypertension is a major Public Health issue. Although the number of treated hypertensive patients has increased, only 25% of treated patients have their blood pressure levels under control. The benefit of treating hypertension has been proven, but cardiovascular morbidity and mortality rates remain high. The ideal antihypertensive drug should not only normalize blood pressure levels, but also reduce the associated cardiovascular morbidity and mortality rates. The role of angiotensin II in systemic hypertension and its complications has been recently redefined. The potent trophic effects of angiotensin II on blood vessels and on cardiac cells have been well demonstrated, especially the role of angiotensin II in left ventricular hypertrophy, vascular hypertrophy, endothelial dysfunction, and congestive heart failure. Of all ongoing mortality and morbidity trials in systemic hypertension, VALUE (Valsartan Antihypertensive Long-term Use Evaluation) is the only one comparing an angiotensin II antagonist (valsartan) with a third-generation calcium channel blocker (amlodipine). The main hypothesis of the VALUE trial is that, for an equivalent decrease in blood pressure, valsartan will be more effective than amlodipine in decreasing cardiac mortality and morbidity. VALUE is a prospective, multinational, multicentre, double-blind, randomized, active-controlled, 2-arm parallel group comparison with a response-dependent dose titration scheme. VALUE involves 14,400 patients in over 30 countries, who will be followed for 4 years or until 1450 patients experience a primary endpoint. The population to be included in VALUE consists of hypertensive men and women, aged 50 years or older, and at a relatively high risk of sustaining a cardiovascular event. The high risk profile is defined taking into account age, gender, and a list of cardiovascular risk factors and disease factors. Risk factors are cigarette smoking, hypercholesterolaemia, diabetes mellitus, uncomplicated left ventricular hypertrophy, proteinuria, and high serum creatinine. Disease factors include documented history of myocardial infarction, peripheral vascular disease, stroke or transient ischaemic attack, or the presence of left ventricular hypertrophy with strain on the ECG. A unique feature of VALUE is the assessment of the predictive power of this cardiovascular risk factor scale in a large population of treated hypertensive patients. The trial started on 10 September 1997.
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PMID:The Valsartan Antihypertensive Long-term Use Evaluation (VALUE) trial of cardiovascular events in hypertension. Rationale and design. 975 88

These experiments examined the effectiveness of chronic blockade of the renin angiotensin system with either valsartan or benazeprilat on survival, blood pressure and end-organ damage in salt-loaded stroke-prone SHR. Valsartan or benazeprilat given continuously by subcutaneous osmotic minipump beginning at 10.5 weeks of age lowered blood pressure, as determined by radiotelemetry, prevented proteinuria, prolonged survival and decreased the severity of histopathological changes in the heart and kidney. These results indicate that angiotensin receptor blockade affords a similar degree of protection as inhibition of angiotensin converting enzyme in salt-loaded stroke-prone SHR. Furthermore, our results are consistent with a primary contribution of angiotensin II to the maintenance of blood pressure and support a principal role for angiotensin II-dependent mechanisms in the development of end-organ damage in the salt-loaded stroke-prone SHR.
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PMID:Protective effects of valsartan and benazeprilat in salt-loaded stroke-prone spontaneously hypertensive rats. 976 21

Hypertension is common in West Africa and likely to become more common as urbanisation increases. There are at present few facilities for the detection and management of hypertension so the influence it has on overall morbidity and mortality in the population is not clear. The objectives of the study were to assess: (a) renal disease and blood pressure related admissions and deaths among acute medical admissions to Komfo Anokye Teaching Hospital, Kumasi, during an 8-month period; and (b) the burden of renal disease among out-patient hypertensives at the same hospital. Ward admission books were examined in the four acute medical wards to ascertain admission diagnosis and cause of death (two 4-month periods in 1995 and 1996). Clinical assessment (blood pressure, plasma creatinine, proteinuria) was also made of 448 consecutive out-patient hypertensives seen between March 1995 and April 1996. Five hundred and ninety-three (17.9%) of 3317 acute medical admissions were ascribable to a cardiovascular cause (hypertension, heart failure, stroke); 171 (28.8%) of these died. One hundred and sixty-six (5.0%) had renal disease of whom 45 (27.1%) died, usually of end-stage renal disease. Among the 448 hypertensive out-patients, 30.2% (110 out of 365) had a plasma creatinine >140 micromol/l (48 > or = 400 micromol/l) and 25.5% (96 out of 376) had proteinuria. Eighty-nine of the 448 had a diastolic blood pressure > or =115 mm Hg; in this group 38 (42.7%) had a plasma creatinine of >140 micromol/l (and 18 or 20.2% > or =400 micromol/l). In conclusion, cardiovascular and renal disease are important contributors to morbidity and mortality among acute medical admissions to a large city hospital in Ghana. Among out-patient hypertensives renal disease is an important complication, especially in those with the more severe hypertension.
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PMID:Hypertension and renal failure in Kumasi, Ghana. 992 50

-The ability of endothelin receptor blockade to prevent and to treat established cerebral and renal injury was explored in salt-loaded stroke-prone spontaneously hypertensive rats (SHRSP) with the endothelin receptor subtype-A antagonist A127722. SHRSP were subjected to 1% NaCl intake. The start of treatment with A127722 (35 and 70 mg. kg-1. d-1, respectively) was either synchronized with salt loading or initiated after the first observation of cerebral edema with T2-weighted magnetic resonance imaging. In untreated control animals median survival was 54 days (range, 32 to 80 days) after the start of salt loading. Early-onset A127722 treatment increased median survival to 233 days (range, 92 to 407 days; P<0.05 versus controls) with 35 mg/kg and to 124 days (range, 97 to 169 days; P<0.05 versus control) with 70 mg/kg. The development of cerebral edema was prevented, and systolic blood pressure and proteinuria were dose-dependently reduced. However, all rats in the 70-mg/kg treatment group developed hemorrhages in the basal ganglia shortly before death. Late-onset A127722 treatment failed to affect survival, systolic blood pressure, or proteinuria. Nevertheless, cerebral edema was reduced but not as well as in early-onset treatment. Development of hypertension, cerebral edema, and proteinuria was prevented in SHRSP when A127722 treatment was initiated at the start of salt-loading. However, A127722 treatment did not prolong survival in SHRSP with cerebral edema. This suggests that in SHRSP the endothelin A receptor participates actively in the development of increased blood pressure and initiation of organ damage but participates minimally in established malignant hypertension and progression of target-organ damage.
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PMID:Early-onset but not late-onset endothelin-A-receptor blockade can modulate hypertension, cerebral edema, and proteinuria in stroke-prone hypertensive rats. 993 Oct 94

Stroke-prone spontaneously hypertensive rats (SHRSP) on 1% NaCl drinking solution and Stroke-Prone Rodent Diet develop severe hypertension and glomerular and vascular lesions characteristic of thrombotic microangiopathy seen in malignant nephrosclerosis. We recently reported that spironolactone, a mineralocorticoid receptor antagonist, markedly reduced proteinuria and malignant nephrosclerotic lesions in these animals. This observation, together with our previous findings that angiotensin-converting enzyme inhibitors prevent the development of vascular damage, suggests that mineralocorticoids, as part of the renin-angiotensin-aldosterone system, play a pathophysiological role in this model. In the present study, we examined whether chronic (2-week) infusion of aldosterone can reverse the renal vascular protective effects of captopril in SHRSP. SHRSP received vehicle (n=8); captopril alone (50 mg. kg-1. d-1, orally) (n=10); aldosterone infusion alone (40 microg. kg-1. d-1, SC) (n=7); or captopril and aldosterone at 20 (n=6) or 40 (n=7) microg. kg-1. d-1. Systolic blood pressure was markedly elevated in all groups. Vehicle- and aldosterone-infused SHRSP developed severe proteinuria and comparable degrees of renal injury (21+/-3% and 29+/-3%, respectively) manifested as thrombotic and proliferative lesions in the arterioles and glomeruli. Captopril treatment reduced plasma aldosterone levels concomitant with marked reductions in proteinuria and the absence of histologic lesions of malignant nephrosclerosis. Aldosterone substitution at 20 or 40 microg. kg-1. d-1 in captopril-treated SHRSP resulted in the development of severe renal lesions (16+/-3% and 21+/-2%, respectively) and proteinuria comparable with that observed in SHRSP given either aldosterone or vehicle alone. These findings support a major role for aldosterone in the development of malignant nephrosclerosis in saline-drinking SHRSP, independent of the effects of blood pressure.
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PMID:Role of aldosterone in renal vascular injury in stroke-prone hypertensive rats. 993 Nov 10

Primary aldosteronism (PA) is widely believed to be a relatively benign form of hypertension associated with a low incidence of vascular complications. However, several recent studies showed that cardiovascular complications were not rare in PA. PA is known as one of the most typical forms of sodium-sensitive hypertension. Recently, we found that the sodium sensitivity of blood pressure was a marker for greater risk for cardiovascular complications, especially stroke, in patients with essential hypertension. Therefore, we investigated cardiovascular complications in 58 patients with PA confirmed to be Conn's adenoma. Cardiovascular complications were found in 34% of 58 patients. Coronary artery disease was found in only one patient (1.7%), as angina pectoris. Stroke was found in nine patients (15.5%), four patients (6.9%) with cerebral infarctions and five patients (8.6%) with cerebral hemorrhages. Proteinuria and renal insufficiency were found in 14 (24.1%) and 4 (6.9%) patients, respectively. The incidence of cerebral infarction and renal insufficiency was greater in men than women. The prevalence of proteinuria was greater in patients with than without stroke (P = 0.03) among those aged older than 40 years. These results indicated that cardiovascular complications, especially stroke and proteinuria, were common in patients with PA, and proteinuria might be an indicator for stroke as target-organ damage.
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PMID:Cardiovascular complications in patients with primary aldosteronism. 1002 36

Data obtained during the last two decades show that spontaneously hypertensive rats, an acceptable experimental model of primary human hypertension, possess increased activity of both ubiquitous and renal cell-specific isoforms of the Na+/H+ exchanger (NHE) and Na+-K+-2Cl- cotransporter. Abnormalities of these ion transporters have been found in patients suffering from essential hypertension. Recent genetic studies demonstrate that genes encoding the beta- and gamma-subunits of ENaC, a renal cell-specific isoform of the Na+-K+-2Cl- cotransporter, and alpha3-, alpha1-, and beta2-subunits of the Na+-K+ pump are localized within quantitative trait loci (QTL) for elevated blood pressure as well as for enhanced heart-to-body weight ratio, proteinuria, phosphate excretion, and stroke latency. On the basis of the homology of genome maps, several other genes encoding these transporters, as well as the Na+/H+ exchanger and Na+-K+-2Cl- cotransporter, can be predicted in QTL related to the pathogenesis of hypertension. However, despite their location within QTL, analysis of cDNA structure did not reveal any mutation in the coding region of the above-listed transporters in primary hypertension, with the exception of G276L substitution in the alpha1-Na+-K+ pump from Dahl salt-sensitive rats and a higher occurrence of T594M mutation of beta-ENaC in the black population with essential hypertension. These results suggest that, in contrast to Mendelian forms of hypertension, the altered activity of monovalent ion transporters in primary hypertension is caused by abnormalities of systems involved in the regulation of their expression and/or function. Further analysis of QTL in F2 hybrids of normotensive and hypertensive rats and in affected sibling pairs will allow mapping of genes causing abnormalities of these regulatory pathways.
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PMID:Genetic and biochemical determinants of abnormal monovalent ion transport in primary hypertension. 1006 78

From the follow-up examination of 1329 out of 4420 type 2 (non-insulin-dependent) diabetes followed for 17 years, the incidence of micro and macrovascular complications (proteinuria and nephropathy, symptoms of leg vascular disease, ischemic heart disease, and cerebrovascular events, was estimated and related to the levels of baseline-risk variables using logistic regression. For new cases of proteinuria and heavy proteinuria, hyperglycemia was the common predictor (alongside diastolic hypertension, smoking and overweight); hyperglycemia and glycosuria were among significant predictors of leg vascular disease (with duration of diabetes, smoking, male sex, diastolic hypertension, and proteinuria). On the other hand, systolic hypertension and male sex prevailed among factors predicting both ischemic heart disease (with high cholesterol and overweight), and stroke. The data confirm the higher involvement of diabetic milieu in micro than macrovascular incidents, with diabetic foot disease placed in between.
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PMID:[Risk factors of the incidence of late vascular complications of diabetes]. 1033 28

The awareness, treatment, and control of hypertension has risen steadily over the past three decades, until the early 1990s. However, blood pressure control to < 140/90 mmHg is attained in fewer than 25% of all hypertensive patients and fewer than 50% of drug-treated hypertensive patients, except for white women. Two special populations, African-Americans and diabetics, share several important attributes. First, they both have a high prevalence of hypertension, including stage 3 hypertension (as defined by the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of Hypertension VI: > or =180/110 mmHg), relative to other subgroups. African-Americans have an approximate 8% prevalence of stage 3 hypertension, and elevated systolic blood pressure is highly prevalent among diabetic people, particularly older African-American women. Second, both groups have high levels of blood-pressure-related target-organ damage, which contributes to their inordinately high absolute risk for cardiovascular disease complications (i.e. stroke, congestive heart failure, renal failure) at a given level of blood pressure. Moreover, the reduced natriuretic capacity common to each group contributes to the attenuated efficacy of antihypertensive drug monotherapy, particularly for drug classes other than diuretics and calcium antagonists. These two special populations are also typically salt-sensitive, an intermediate blood pressure phenotype that raises blood pressure medication requirements. This phenomenon has been associated with an attenuation in the normal nocturnal fall in blood pressure. The high absolute risk for cardiovascular disease among diabetics led to the formulation of more aggressive treatment recommendations for antihypertensive drug therapy. In diabetics, blood pressure therapy is initiated at blood pressures > or = 130/85 mmHg, and treatment goals are at least to this level, unless proteinuria is > or = 1g/day (in which case the goals are < 125/75 mmHg). The more aggressive treatment targets for diabetics will not be reached with most currently available single antihypertensive agents in many African-Americans. While at best only 50-60% of hypertensive patients can be controlled with single drug therapy, that percentage falls dramatically in persons with stage 3 hypertension and renal insufficiency, thereby necessitating the use of combination drug therapy. Treatment alone is not enough; treatment to goal blood pressure is an essential first step towards optimal target-organ protection. While circulating levels of renin are suppressed, in general, in these special populations, each group manifests an inordinate burden of blood-pressure-related target-organ damage that has been linked to excessive levels of angiotensin II or a reduced bradykinin and nitric oxide tissue effect. The renin-angiotensin-aldo-sterone-kinin system is therefore an attractive therapeutic target that might conceivably provide target-organ protection over and above that attributable solely to lowering the blood pressure.
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PMID:Difficult-to-treat hypertensive populations: focus on African-Americans and people with type 2 diabetes. 1034 Aug 40


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