Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

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.
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PMID:Endothelin-receptor antagonists in uremic cardiomyopathy. 1107 17

We report on a 4-year-old girl with hyponatremic-hypertensive syndrome (HHS), a rare entity in childhood. The girl was referred to us from a local hospital with a history of recurrent fever, vomiting, and seizures. On admission she was markedly dehydrated. Initial investigations revealed severe hyponatremia (serum Na 120 mmol/l), hypochloremia (serum Cl 68 mmol/l), and mild hypokalemia (serum K 3.3 mmol/l), while serum calcium and magnesium were normal. Serum urea was 5 mmol/l and serum creatinine was 62 mumol/l. Despite hyponatremic dehydration, her urine output was high (2050 ml/24 h), as was her urinary sodium (168 mmol/24 h). She had massive transient proteinuria (maximal 1642 mg/24 h) while being severely hypertensive (blood pressure 210/160 mmHg). Further investigations revealed right kidney scarring, hyper-reflexive bladder dysfunction, massive brain infarcts, and myocardial left ventricular hypertrophy. Renal arteries were normal on arteriography. Blood pressure control resulted in normalization of serum and urinary electrolytes and decrease of proteinuria. Hyponatremia and transient massive proteinuria in this patient seem to be caused by high-pressure-forced diuresis due to malignant renoparenchymal hypertension.
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PMID:Hyponatremic hypertensive syndrome. 1114 28

We previously reported that inhibition of angiotensin-converting enzyme (ACE) prevented the hypertension and left ventricular hypertrophy induced by deoxycorticosterone acetate-salt (DOCA-salt) in 129/SvEvTac mice, which have 2 renin genes (Ren-1 and Ren-2). In the present study, we induced hypertension by uninephrectomy and DOCA-salt in mice having only the Ren-1 gene (C57BL/6J) and investigated the effect of an ACE inhibitor (ramipril, 4 mg. kg(-)(1). d(-)(1)) and an angiotensin type 1 (AT(1)) receptor antagonist (L-158809, 4 mg. kg(-)(1). d(-)(1)) on the development of hypertension, cardiac hypertrophy, and renal injury. After 4 weeks of treatment, systolic blood pressure in DOCA-salt mice was significantly increased (128+/-2 mm Hg) compared with controls (109+/-2 mm Hg) (P:<0.001), while plasma renin concentration was decreased by 97% (P:<0.001). DOCA-salt also induced left ventricular and renal hypertrophy and renal damage as manifested by proteinuria. Collagen content in the left ventricle and kidney was significantly higher in DOCA-salt mice (P:<0.001). Urinary albumin (P:<0.05) and proliferating cell nucleic antigen-positive cells in the tubules and interstitium of the renal cortex (P:<0.001) were significantly increased in the DOCA-salt group. Neither the ACE inhibitor nor the AT(1) antagonist had any antihypertensive effect; however, they partially prevented cardiac hypertrophy and completely inhibited left ventricular collagen deposition. In the kidney, both the ACE inhibitor and AT(1) antagonist partially reduced the increase in collagen but had no effect on hypertrophy. They also significantly prevented the effect of DOCA-salt on urinary albumin and proliferating cell nucleic antigen expression in the kidney. Despite the lack of an antihypertensive effect, both ACE inhibitor and AT(1) antagonist prevented cardiac remodeling and renal damage. Our results indicate that ACE inhibitors and AT(1) antagonists exert beneficial effects on the heart and kidney in DOCA-salt hypertensive mice independently of their effects on blood pressure.
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PMID:Effects of angiotensin-converting enzyme inhibitor and angiotensin type 1 receptor antagonist in deoxycorticosterone acetate-salt hypertensive mice lacking Ren-2 gene. 1124 26

Fixed verapamil SR/trandolapril combinations 180/1 mg and 180/2 mg (Tarka, Knoll AG) have a significantly superior antihypertensive effect compared to equal dosages of either agent alone. Verapamil SR/trandolapril 180/2 mg combination produces the best dose-response ratio of different dose combinations of these two drugs. Combination therapy has the most pronounced effect on blunting the early morning rise in blood pressure. Thus, verapamil SR/trandolapril combination therapy may be an appropriate treatment option in patients with moderate essential hypertension, particularly in those who have a tendency toward the early morning rise in blood pressure. The adverse effect profile of the fixed combination of verapamil SR/trandolapril includes the typical side effects of its monocompounds. The fixed combination of verapamil SR/trandolapril is also effective and safe in the treatment of hypertension in the elderly. The fixed low-dose combination therapy with verapamil SR/trandolapril 180/2 mg is a suitable treatment option for patients with moderate essential hypertension and Type 2 diabetes mellitus, because it improves parameters of carbohydrate metabolism and uricaemia and does not alter the lipid profile. The insulin-sensitising effect of angiotensin converting enzyme (ACE) inhibitor monotherapy with its theoretical risk of hypoglycaemia is completely neutralised in the combination with verapamil SR. Comparative studies have shown that the low-dose combination of verapamil SR/trandolapril may be a suitable alternative to combinations containing a thiazide diuretic or a beta-blocking agent for the long-term management of hypertensive patients for whom combination therapy is indicated. The combination of an ACE inhibitor with a non-dihydropyridine calcium channel blocker reduces proteinuria to a greater extent than either agent alone. A combination of an ACE inhibitor and a calcium channel blocker may provide additional benefit in inducing the regression of left ventricular hypertrophy. Combination therapy leads to a significant increase in left ventricular ejection fraction, improvement of wall motion index and increases exercise duration time in patients with coronary heart disease and left heart failure. It also improves the ratio of exercise to rest rate-pressure product and decreases the number of angina attacks. These findings support the hypothesis that the combination of verapamil and trandolapril might be useful in patients with attenuated left ventricular function and angina pectoris. Thus, Tarka is an effective and well-tolerated antihypertensive agent with a good safety profile and positive metabolic effects.
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PMID:The fixed combination of verapamil SR/trandolapril. 1124 35

The management of diabetic hypertension requires meticulous selection of agents in the antihypertension armamentorium. There may be several associated factors to be considered while treating a hypertensive diabetic. These include hyperglycemia, dyslipidemia, proteinuria, left ventricular hypertrophy and heart failure to name a few. Losartan is the first of a new class of agents in the list of antihypertensive drugs. By its selective angiotension II receptor (subtype AT1) blocking action it is postulated to bring about a more complete inhibition of the renin-angiotensin system. Thus, it might produce all the benefits of angiotensin converting enzyme (ACE) inhibitor therapy with the freedom from cough so commonly seen with the use of ACE inhibitors. This review attempts to analyze the possible benefits of losartan therapy in diabetes.
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PMID:Role of losartan therapy in the management of diabetic hypertension. 1127 47

Although the relation between the blunted nocturnal decline in blood pressure and target organ damages is well established, the mechanism underlying these results has not been clarified. We investigated the relationship among heart rate variability, nocturnal change in blood pressure and the severity of cardiac and extracardiac target organ damages caused by essential hypertension. We studied 52 Japanese inpatients with essential hypertension (24 men and 28 women; mean age, 49+/-3 years). After a stabilization period of 1 week, ambulatory blood pressure monitoring (ABPM) and 24-h ECG monitoring were performed and analyzed. The non-dipper subjects were defined as those whose nocturnal decrease of mean BP was < 10% of daytime blood pressure (BP). The sex, age, body mass index. duration of hypertension, and 24-h BP were similar in dipper (n = 34) and non-dipper (n = 18) patients. The left ventricular mass index (LVMI) was significantly higher and the degree of hypertensive retinopathy was significantly worse in the non-dipper patients than that of the dipper patients. In the non-dipper patients, indexes of time-domain analysis such as the sum of differences between adjacent RR intervals (NNDrms), the number of pairs of adjacent RR intervals differing by more than 50 ms in the entire recording (RR 50) were significantly lower than that of the dipper patients. Additionally, as for spectral analysis, daytime low frequency/high frequency (LF/HF) was higher and nighttime high frequency (HF) was lower than that of the dipper patients. Independent predictors were the 24-h mean blood pressure (MBP) for left ventricular hypertrophy (LVH), nighttime systric BP (SBP) for progress in retinopathy and duration of hypertension for proteinuria. In conclusion, decrease in parasympathetic nervous function and increase in sympathetic nervous function may contribute to occurrence of non-dipper phenomenon, as well as progress in retinopathy.
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PMID:Non-dipper phenomenon in essential hypertension is related to blunted nocturnal rise and fall of sympatho-vagal nervous activity and progress in retinopathy. 1147 60

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.
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PMID:Influence of multiple risk factors on the hazard of hypertension. 1152 37

The angiotensin-converting enzyme inhibitor, perindopril erbumine, has been approved for use in the United States only recently but has been studied extensively worldwide over the last decade. Placebo-controlled trials in a wide range of patients with hypertension, including the elderly, those with isolated systolic hypertension, and those with concomitant diseases such as hyperlipidemia, diabetes, cardiac arrhythmia, peripheral arterial occlusive disease, nephropathy with proteinuria, and chronic obstructive pulmonary disease, have shown that perindopril is highly effective in lowering both systolic and diastolic blood pressure (BP). Studies in which BP has been monitored for 24-hour intervals show that perindopril (1) has a gradual onset of action, (2) provides smooth BP control over its once-daily dosing interval, (3) has a trough-peak ratio of about 1, and (4) maintains its antihypertensive efficacy despite missed doses. Perindopril increases arterial compliance and reverses left ventricular hypertrophy in hypertensive patients. Both of these effects are at least partly independent of its ability to lower BP. Perindopril is safe and well tolerated in patients with hypertension. Rates of adverse events and discontinuation because of such events are low.
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PMID:Efficacy of perindopril in the treatment of systemic hypertension. 1159 55

The aim of the present study is to investigate the pathophysiological characteristics of a number of recent cases of malignant hypertension (MHT) and to compare them to the characteristics of earlier cases. Patients with MHT (age 25-76, mean 44+/-2 years) who were admitted to our hospital from 1984-1999 were retrospectively studied. All of the patients had either grade III or IV retinopathy and diastolic blood pressure levels higher than 120 mmHg. The observations in this study were compared to previously reported findings regarding 59 MHT patients who were admitted from 1971-1983. Of the 37 recent MHT patients, 20 had essential hypertension (EHT) as the underlying disease, 13 had chronic glomerulonephritis (CGN), and the remaining 4 presented with other diseases including pyelonephritis and renovascular hypertension. A positive family history of hypertension was more prevalent in the EHT patients than in other patients, and persistent proteinuria, microhematuria, and anemia were more prevalent in the CGN patients. These characteristics were similar between the recent and previous cases. Within 4 weeks after admission, hemodialysis was initiated in 3 of the 13 patients (23%) with CGN and 2 of the 20 (10%) patients with EHT. The prevalence of renal death at 1 year after admission was 30%, which was lower than the prevalence in the previous cases (42%). Grade IV retinopathy was seen in 45% of the patients admitted from 1984-1999, significantly less than in the patients admitted from 1971-1983 (66%, p<0.05). In addition, left ventricular hypertrophy was less frequently observed on electrocardiogram in the recent cases (67%) than in the previous cases (88%, p<0.05). Our results suggest that the recent cases of MHT demonstrate less severe organ damage.
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PMID:Trends in the pathophysiological characteristics of malignant hypertension. 1167 41

The aim of the CASTEL, a population-based (n=3282) prospective study which began 14 years ago, was to identify those items which had a prognostic impact in the elderly, and to evaluate whether the typical cardiovascular risk factors, particularly arterial hypertension, play a role after the age of 65 years. Initial screening, final follow-up and annual detection of mortality were performed. Mantel-Hanszel approach and multivariate Cox model were used for statistics. Cardiovascular mortality was 23.3% in normotensive, 23.3% in borderline, and 25% in the sustained hypertensive subjects (insignificant difference). In women, the incidence of stroke and coronary artery disease weakly depended on pulse pressure. Historical stroke and myocardial infarction predicted cardiovascular mortality in women; diabetes, uricaemia and high heart rate in men. In the very old, the predictors were less numerous, and blood pressure was not a predictor whatsoever; pulse blood pressure and murmurs at the neck were especially predictive in women, historical heart failure, proteinuria and tachycardia in men, historical stroke and myocardial infarction, pulmonary disease, left ventricular hypertrophy, diabetes and uricaemia in both genders. The elderly have a different cardiovascular risk pattern compared to younger people. Hypertension is not a predictor of coronary and stroke mortality. Prognosis depends on pulse pressure rather than on the label 'hypertension'. Hypercholesterolaemia is not a risk factor. This could simply indicate that elderly persons are the survivors in a population where significant mortality has already made its mark, eliminating those with the worst risk pattern. The two genders have a different risk profile due to sex-specific susceptibility to risk factors.
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PMID:Weak effect of hypertension and other classic risk factors in the elderly who have already paid their toll. 1184 Feb 26


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