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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The long-term effects of converting enzyme inhibitors and calcium channel blockers on proteinuria and the progression of renal disease in patients with hypertension and chronic renal insufficiency are not well established. We have studied the long-term effects of treating hypertension with an angiotensin-converting enzyme inhibitor, enalapril, and a calcium channel blocker, nicardipine, on urinary albumin excretion (UAE) and on renal function in 16 patients with hypertension and chronic renal insufficiency (creatinine clearance ranging between 17 and 62 ml/min). After 1 year of treatment, these agents caused a similar decrease in blood pressure. Only enalapril, however, caused a significant decrease in UAE (from 641 +/- 98 to 292 +/- 47 mg/24 h, p less than 0.01), whereas UAE did not change in the group treated with nicardipine (675 +/- 78 vs. 601 +/- 75 mg/24 h). Creatinine clearance at the beginning of the study was similar in the group treated with enalapril and in the group treated with nicardipine (35 +/- 3.6 vs. 40 +/- 4.1 ml/min). After 1 year of follow-up, creatinine clearance remained unchanged in both groups of patients. These studies demonstrate that both enalapril and nicardipine can effectively reduce blood pressure in patients with hypertension and chronic renal insufficiency. Enalapril but not nicardipine, however, appears to reduce urinary albumin excretion in these patients. Whether the reduction in UAE has any significant impact on the progression of renal disease remains to be established.
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PMID:Long-term effects of enalapril and nicardipine on urinary albumin excretion in patients with chronic renal insufficiency: a 1-year follow-up. 195 74

The effect of chronic angiotensin I converting enzyme inhibition on the pressure-natriuresis relation was studied in Wistar-Kyoto and spontaneously hypertensive rats. Enalapril maleate (25 mg.kg-1.day-1 in drinking water) was started at 4-5 weeks of age. At 7-9 weeks of age, the pressure-natriuresis relation was studied while the rats were under Inactin anesthesia 1 week after the right kidney and adrenal gland were removed. Neural and hormonal influences on the remaining kidney were fixed by surgical renal denervation, adrenalectomy, and infusion of a hormone cocktail (330 microliters.kg-1.min-1) containing high levels of aldosterone, arginine vasopressin, hydrocortisone, and norepinephrine dissolved in 0.9% NaCl containing 1% albumin. Changes in renal function resulting from alterations in renal artery pressure were compared between enalapril-treated and control rats. Mean arterial pressure (+/- SEM) under anesthesia was 118 +/- 5, 94 +/- 4, 175 +/- 3, and 124 +/- 2 mm Hg for control Wistar-Kyoto (n = 10), enalapril-treated Wistar-Kyoto (n = 10), control spontaneously hypertensive (n = 9), and enalapril-treated spontaneously hypertensive (n = 9) rats, respectively. When renal artery pressure was set at values above approximately 125 mm Hg, control spontaneously hypertensive rats excreted less sodium and water than control Wistar-Kyoto rats. Enalapril treatment resulted in a significant and similar shift to the left of the pressure-natriuresis relation in both strains of rats so that a lower renal artery pressure was required to excrete a similar amount of sodium when compared with their respective untreated controls.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1991 Jan
PMID:Effect of enalapril treatment on the pressure-natriuresis curve in spontaneously hypertensive rats. 198 83

Enalapril produces an inhibition of the angiotensin-renin system, correlating the pre-therapy plasmatic renin activity with blood pressure decrease, during its administration. This does not always happen, data to the contrary existing in literature, suggesting that there are some other acting mechanisms. We studied 34 hypertensive patients, whose blood pressure levels were controlled by Enalapril at a mean dosage of 12.32 +/- 0.9. Determining plasmatic concentration of 6-keto PGF1a (a prostacyclin metabolite), T x B2 (a thromboxane A2 metabolite), their distribution, plasmatic renin activity and a radiological and biochemical study. We found a significant increase in their distribution and plasmatic renin at the end of the essay. The results suggest a possible double active mechanism: angiotension-renin and prostaglandins systems, owing to the imbalance occurring between prostacyclin and thromboxane, the first named being the most favoured. This, together with easy application and the lack of side effects, made this drug useful for treatment of blood hypertension.
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PMID:[The role of prostacyclin and thromboxane in the antihypertensive action of enalapril]. 210 19

The effect of long-term therapy of hypertension with antihypertensive drugs was investigated in 117 previously untreated patients (15 women, 102 men; mean age 46.4 +/- 9 years) with echocardiographically proven left-ventricular hypertrophy. 22 patients (group 1) received 100 mg/d Gallopamil, 25 (group 2) received 200 mg/d Metoprolol, 35 daily received both 50 mg Atenolol and 20 mg Nifedipine (group 3), 14 received daily 200 mg Acebutolol plus 20 mg Nifedipine (group 4), and 21 (group 5) 50 mg Atenolol plus 10 mg Enalapril daily. The treatment period lasted a mean of 38 (36.2-42.3) months. Left-ventricular muscle mass index (LVMI) as well as septal and posterior-wall thickness decreased significantly after 12.8 and 38.5 months (P less than 0.001). After a mean of 38.5 months LVMI had decreased by 36.7% in group 1, 35.1% in group 2, 42.3% in group 3, 45% in group 4 and 39.6% in group 5. LVMI was within normal range (less than or equal to 95 g/m2) in 81 of the 117 patients (69.2%) at the end of the treatment period. There was, however, no significant increase of the end-diastolic dimension of the left ventricle, but a significant increase of "fractional shortening" as a measure of myocardial contractility.
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PMID:[Regression of left ventricular hypertrophy in hypertensive patients under long-term therapy with antihypertensive agents]. 213 9

The urinary albumin excretion measured by the albumin creatinine clearance ratio (Calb/Ccreat) and the mean supine arterial blood pressure (MAP) were studied before the start of ACE inhibition, at the start and during up to 1 year of ACE inhibition with Captopril or Enalapril in 35 patients with various chronic proteinuric renal disorders with or without renal failure, arterial hypertension and nephrotic syndrome. Before the start of ACE inhibition mean Calb/Ccreat, MAP, s-albumin and s-creatinine did not change. During ACE inhibition the Calb/Ccreat was reduced from 75% (p less than 0.05) in patients with minimal albuminuria to 41% (p less than 0.005) in patients with extensive albuminuria. Average reduction of albuminuria was 44% at one year's observation time. Serum albumin increased 9% (p less than 0.05), serum creatinine did not change significantly and MAP showed a slight, not uniformly significant decrease. The reduction of Calb/Ccreat was of the same order in the different renal disorders studied and was independent of the renal function, presence or absence of nephrotic syndrome and treatment with antihypertensive or immunosuppressive drugs. The decrease in Calb/Ccreat during ACE inhibition was related to the reduction in MAP at most time intervals, but Calb/Ccreat decreased also when MAP was unchanged or increased. Thus the decrease in Calb/Ccreat during ACE inhibition does not only seem to be a consequence of a decrease in the systemic arterial blood pressure but reasonably also due to changes in the intra-renal hemodynamics and most probably a decrease in the glomerular capillary pressure.
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PMID:Reduction of albuminuria after angiotensin converting enzyme inhibition in various renal disorders. 218 37

The long-term antihypertensive effects of enalapril were assessed for a period of up to 1 year in 44 elderly patients with mild-to-moderate essential hypertension. Following a 2-week placebo period, patients who were assigned to enalapril were followed for 6 weeks in a randomized clinical trial. In patients who benefited from enalapril, treatment was continued and subjects were followed for up to 1 year. Supine and standing systolic and diastolic blood pressures were significantly reduced throughout the 1-year period compared with baseline. The dosage of enalapril was increased from 10 to 20 mg daily in 12 patients; 8 required additional antihypertensive agents. Enalapril is effective in the long-term treatment of hypertension; no loss of antihypertensive agents. Enalapril is effective in the long-term treatment of hypertension; no loss of antihypertensive effect occurs.
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PMID:Enalapril in the long-term treatment of elderly hypertensives. 218 77

The safety and antihypertensive effectiveness of a fixed-dose combination form of spironolactone + altizide (S/A) were compared with those of enalapril, an angiotensin-converting enzyme inhibitor in a randomized, double-blind, parallel-group study of 186 patients with moderate essential hypertension. The 2 treatment groups were comparable in terms of age, gender, duration and severity of hypertension, diastolic blood pressure (BP), serum potassium and creatinine, and 24-hour urinary sodium excretion after a 4-week washout phase. After 8 weeks of treatment, both S/A and enalapril decreased BP significantly and to about the same extent. Enalapril, however, was more effective in decreasing supine diastolic BP in patients younger than age 50, whereas S/A yielded better results in those older than 50. Laboratory values were similar after both drugs were administered, and there were no clinically significant changes. The study demonstrated that S/A safely reduces elevated BP, particularly in older patients.
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PMID:Spironolactone and altizide versus converting enzyme inhibitor (enalapril). 219 86

The orally active angiotensin-converting inhibitors (ACE inhibitors) such as captopril and enalapril represent a significant therapeutic advance in the treatment of hypertension and congestive heart failure. Enalapril differs from captopril in several respects. It is a prodrug converted by hepatic esterolysis to the active (but more poorly absorbed) diacid, enalaprilat. Enalaprilat is more potent than captopril, more slowly eliminated and does not possess a sulfhydryl (SH) group. Enalapril was rapidly followed by a number of newer ACE inhibitors, the majority of which are similar to enalapril in that they are prodrugs, converted by hepatic esterolysis to a major active but poorly absorbed diacid metabolite. In one case (delapril) there are 2 active metabolites; in another (alacepril) the prodrug is converted in vivo to captopril. Lisinopril is an exception in that it is an enalaprilat-like diacid but with acceptable oral bioavailability, so that the prodrug route is not employed. The newer ACE inhibitors are at widely different stages of development, and it is not yet clear how many will reach regular clinical use. Of these newer drugs, lisinopril is the longest established and is the subject of the widest published literature. For a number there is as yet little published pharmacokinetic information. A variety of assay methods have been employed to characterise the pharmacokinetics of the ACE inhibitors, including enzymatic techniques, radioimmunoassay and chromatography. The peak plasma concentrations of the prodrugs are generally observed at around 1 hour and those of the diacid metabolites at about 2 to 4 hours. However, there is considerable variation within and between drugs, with benazepril and benazeprilat reaching peak concentrations early and enalapril and enalaprilat typical of later times to peak. Absorption of the active diacids is generally poor, and moderate (typically 30 to 70%) for the prodrugs. The bioavailability of lisinopril is about 25%. It is difficult to talk meaningfully about half-lives of the active drugs. The declines in their plasma concentrations are polyphasic and, if analytical sensitivity allows, active drug may be found at 48 hours or more following administration. This may reflect binding to ACE in plasma. Half-lives of accumulation are of the order of 12 hours; protein binding varies from little (lisinopril) to 90% (benazeprilat). Elimination is mostly renal but there may be biliary elimination for some, such as benazeprilat and fosinopril. The half-lives of the prodrugs are short. Impaired renal function decreases the elimination rate of the diacids.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Clinical pharmacokinetics of the newer ACE inhibitors. A review. 220 79

The effect of enalapril was evaluated in 67 patients with essential hypertension, and its therapeutic efficacy was compared with atenolol in a placebo run-in, single-blind, cross-over trial. Enalapril significantly reduced blood pressure in all grades of essential hypertension. As monotherapy it 'normalized' blood pressure in 88%, 50% and 25% of patients with mild, moderate and severe hypertension respectively. Optimal dose for most of the patients was 20 to 40 mg/day. Comparison with atenolol revealed almost parallel efficacy of the two drugs, although enalapril produced a significantly greater reduction in systolic blood pressure in patients with mild and moderate hypertension (P less than 0.01 in each group). No serious side effects were encountered with either drug. Enalapril, therefore, has a potent and slightly superior antihypertensive effect to that of atenolol, and may be used as a 'first-step' drug in the treatment of hypertensive patients.
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PMID:Efficacy of enalapril in essential hypertension and its comparison with atenolol. 221 94

Rats of the spontaneously hypertensive strain develop kidney damage that resembles the nephropathy seen in some cases of human essential hypertension. Previous studies with a triple drug antihypertensive regimen indicated that proteinuria and glomerular histopathology in spontaneously hypertensive rats might develop despite long-term effective control of systemic blood pressure. To investigate further the relation between hypertension and kidney disease, a group of spontaneously hypertensive rats were treated with enalapril at 15 weeks of age. Blood pressure, protein excretion, and kidney function were measured in those rats at regular intervals during the next year and a half and were compared with untreated spontaneously hypertensive rats and the normotensive Wistar-Kyoto parent strain. Kidney tissue samples from all three groups, collected at autopsy, were stained by immunohistochemical and conventional methods to assess the relative severity and nature of kidney damage. Although enalapril therapy was completely effective in controlling the blood pressure of spontaneously hypertensive rats, it only postponed the onset of kidney disease. Enalapril-treated spontaneously hypertensive rats eventually exhibited albuminuria as severe as that found in hypertensive rats. Kidney vessel pathology was completely prevented with enalapril, but the abnormal accumulation of mononuclear cells in tubulointerstitial and periglomerular sites was the same as in untreated spontaneously hypertensive rats. We have concluded that elevated protein excretion in rats of the spontaneously hypertensive rat strain is not a secondary consequence of systemic hypertension. Structural abnormalities of renal vessels also do not appear to contribute significantly to the pathogenesis of albuminuria in spontaneously hypertensive rats. Other explanations must be sought to account for the close link between spontaneous hypertension and kidney damage in this animal model. The clear dissociation of kidney disease from systemic hypertension exhibited by spontaneously hypertensive rats may also be relevant for human disease.
Hypertension 1990 Nov
PMID:Enalapril and renal injury in spontaneously hypertensive rats. 222 55


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