Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The activation of the sympathetic nervous system and the renin-angiotensin-aldosterone system and its beneficial modification with the use of angiotensin-converting enzyme inhibin after inferior wall myocardial infarction (MI) was evaluated. Fifty patients with acute inferior MI were randomly assigned to receive 5 mg per day of either enalapril or placebo after admission. Blood tests for neurohormone levels and echocardiograms were performed at initial examination and 4 weeks later. Baseline characteristics were similar in the two groups. Four weeks after randomization, patients treated with enalapril had lower end-diastolic volume (146 +/- 29 vs 167 +/- 15 ml; p = 0.04), end-systolic volume (56 +/- 18 vs 107 +/- 17 ml; p = 0.03), serum norepinephrine levels (320 +/- 93 vs 465 +/- 77 pg/ml; p < 0.01), angiotensin II levels (18 +/- 6 vs 54 +/- 11 pg/ml; p < 0.01), and atrial natriuretic polypeptide levels (106 +/- 9 vs 122 +/- 17 pg/ml; p = 0.05) than patients given placebo. The incidence of heart failure after MI was also lower in this group (4% vs 16%; p = 0.009). Results show that there is early neurohumoral activation in the course of acute inferior wall MI. Enalapril reduces neurohumoral levels and preserves ventricular volumes. These effects were associated with a reduction in the incidence of heart failure 4 weeks after MI in these patients.
 ...
PMID:Effects of enalapril on ventricular volumes and neurohumoral status after inferior wall myocardial infarction. 847 46

Drug induced modification of the renin-angiotensin system is of established benefit in the treatment of hypertension and heart failure. The responses to the angiotensin converting enzyme (ACE) inhibitor enalapril (CAS 75847-73-3) have been studied in essential hypertension and normotensive controls. The kinetics and dynamics of enalapril have been characterised in an integrated concentration-effect model to identify factors underlying responsiveness to the ACE inhibitor. In addition models to predict the response to long-term treatment from changes after the first dose have been developed. Enalapril response could be described by a non linear (Emax) model defined by two parameters - the maximum response (Emax) and the drug concentration required to cause 50% of the maximum response (C50). Acute dosing accurately predicted the Emax after 6 weeks treatment. In addition to individual pharmacokinetics, pretreatment blood pressure was the most important determinant of response to enalapril. In caucasian salt-replete essential hypertension neither age nor plasma renin activity were major factors. However, in states of sodium restriction and/or diuretic treatment, the response to enalapril was greatly increased. The angiotensin II receptor antagonist, losartan has been reported to be without effect on blood pressure in salt-replete normals. Salt restriction together with furosemide for 3 days led to dose-related falls in blood pressure in normal subjects after losartan 25-100 mg. Concentration-effect analysis can be used to describe blood pressure responses, to predict the responses to long-term treatment and also to identify quantitatively important factors determining the response in individual patients.
 ...
PMID:Inhibitors of the renin-angiotensin system. Clinical pharmacology studies on kinetics, dynamics and concentration-effect relationships. 849 75

The hereditary cardiomyopathic strain of Syrian hamster has been extensively studied as a model of cardiomyopathy of heart failure. We attempted to determine whether an angiotensin converting enzyme (ACE) inhibitor, enalapril, prevents the increase in extracellular collagen matrix which connects the myocytes in cardiomyopathy. Enalapril was administered at an average dosage of 10 mg/kg per day to 10- to 20-week-old hamsters with hypertrophic (Bio 14.6) and dilated (Bio 53.58) cardiomyopathy, as well as to control Syrian hamsters (F1 beta). Collagen concentration estimated by hydroxyproline concentration and the collagen type III:I ratio significantly increased in the hearts of the Bio 14.6 and Bio 53.58 strains at 20 and 40 weeks of age as, compared with those in age-matched F1 beta hamsters. When Bio 14.6 hamsters were given enalapril for 10 weeks from 10 to 20 weeks of age, the collagen concentration, the collagen type III:I ratio and type III collagen mRNA expression were significantly decreased, compared with those in untreated animals of the same strain. After the administration of enalapril, scanning electron microscopic examination also revealed a decrease in fibrillar collagen accumulation in the interstitium and the network surrounding the cardiac myocytes. These prophylactic effects were not observed in the Bio 53.58 strain. These results indicate that the administration of ACE inhibitor prevents type III collagen production in the Bio 14.6 strain but not in the Bio 53.58 strain of Syrian hamster.
 ...
PMID:Effects of enalapril on the collagen matrix in cardiomyopathic Syrian hamsters (Bio 14.6 and 53.58). 864 84

Enalapril is widely prescribed for hypertension and cardiac failure. Rashes are an uncommon side-effect, occurring in approximately 1.4% of patients, and in approximately 0.4% of patients the rash is sufficient to require discontinuation of enalapril. (Merck Sharp and Dohme, pers. comm.) We report a case of toxic pustuloderma related to enalapril therapy for congestive cardiac failure. To our knowledge enalapril-induced toxic pustuloderma has not been previously reported.
 ...
PMID:Enalapril-induced toxic pustuloderma. 868 72

Our hypothesis is that regulation of the lung vessel tone and microvascular permeability may be disrupted in chronic heart failure (CHF) and angiotensin converting enzyme (ACE) inhibition may contribute to their readjustment. This hypothesis is based on the fact that KII-ACE, the same enzyme that converts angiotensin I and inactivates bradykinin, is highly concentrated in the luminal surface of the lung vessels and its blockade in CHF may reduce their exposure to an excess of angiotensin II and augment the action of prostaglandins and nitric oxide (NO) deriving from local kinin hyperconcentration. We probed whether ACE-inhibitors influence the pulmonary function; this is peculiar of CHF; they act as KII- or ACE-blockers. Aspirin was utilized as a prostaglandin synthesis inhibitor. We investigated 16 CHF patients and 16 age- and sex-matched normal volunteers or mild untreated hypertensives. All were non-smokers, not taking ACE-inhibitors, aspirin or other cyclooxygenase inhibitors. Pulmonary function tests, exercise testing with respiratory gases and echocardiography were performed in the run-in and repeated at the end of placebo, enalapril (10 mg t.i.d.), enalapril plus aspirin (325 mg/day) and aspirin given in random order and double-blind fashion for 15 days each. Enalapril, as compared to placebo, caused an increase in mean voluntary ventilation (MVV) and alveolar-capillary diffusing capacity for carbon monoxide (DLCO) in CHF, that were counteracted by the addition of aspirin. Aspirin alone was not effective. Enalapril and aspirin were ineffective on the pulmonary function of controls. As to the functional capacity, enalapril increased exercise tolerance time, oxygen consumption (VO2p), minute ventilation (VEp) tidal volume (VTp) and reduced the ratio of volume of dead space gas (VDp) to VTp (VD/VTp), at peak exercise in CHF patients. These effects all were inhibited by the combination of aspirin and were not observed in controls. In CHF VO2p changes from placebo correlated with those in DLCO (r = 0.80, p < 0.0001) and not with those in ejection fraction. This correlation was abolished by aspirin and was not seen in controls. Variations in VD/VTp in CHF patients while on enalapril were related to those in DLCO (r = -0.69, p = 0.003). In CHF the ventilatory equivalent for carbon dioxide production per minute at 1 liter was diminished with enalapril and not in combination with aspirin. Derangements related to CHF are the substrate for benefits of ACE-inhibition on pulmonary function and exercise capacity. Pulmonary diffusion limitation is an important mediator of exercise impairment and its improvement with enalapril goes in parallel with VD/VT, MVV, VT, VE to VCO2 relationship and not with ejection fraction. These patterns reflect changes occurring within the lung that are not related to left ventricular function. The counteracting influence of aspirin on these affects bespeaks a substantial participation of prostaglandins that might readjust capillary permeability and lung interstitial fluid content or alveolar capillary membrane diffusing capacity.
 ...
PMID:[Acetylsalicylic acid antagonism vs ACE inhibitor in congestive heart failure as shown by a diminished respiratory and exercise capacity]. 876 15

ACE-inhibitors are used in the treatment of hypertension, and ischemic heart disease, chronic heart failure, cardiomyopathy and diabetic nephropathy. The effect of the ACE inhibitors is mainly due to the inhibition of the angiotensin converting-enzyme, but they also potentiate the effect of bradykinine. Sargent et al. have indicated, that SH-containing ACE-inhibitors show an effect on KATP-channel open probability in vascular smooth muscle. In our experiments, we used isolated bovine coronary arteries and guinea pig aortas, which were cut transversally and brought into Normal-Tyrode-solution. The vessels were precontracted with phenylephrine or U 46619, and after that a cumulative dose of the SH-containing ACE-inhibitors Captopril or Zofenopril was added to obtain a relaxation curve. In a second series we blocked the KATP-channels with glibenclamide to see if the relaxation could be attenuated. In bovine coronary arteries the relaxing effect of Captopril could not be attenuated by glibenclamide, a specific blocker of KATP-channels of vascular smooth muscle. In the guinea pig aorta, the relaxing effect of Zofenopril was also not effected by glibenclamide. The concentrations of Zofenopril were between 10(-7) and 10(-4) mol/l; the maximal effect could be seen at a concentration of 10(-5) mol/l. Experiments with the non SH-containing ACE-inhibitor Enalapril did also not show any statistically significant difference between the 2 groups of series. We conclude, that, in contrast to Sargent's conclusions, there is little or no effect on KATP-channels due to the presence of SH-groups.
 ...
PMID:[ACE inhibitors with SH groups have no effect of ATP-dependent K channels--a dissertation]. 896 87

We tested the hypothesis that concurrent inhibition of the renin angiotensin system by enalapril (5 mg) and the sympathetic nervous system by alpha 1 adrenergic blockade (prazosin 1 mg) will be superior to enalapril alone in 17 patients with heart failure on standard therapy, in a single blind, placebo-controlled, randomized parallel group study for 4 weeks. Enalapril alone induced a significant increase in exercise time from 499 +/- 412 s to 707 +/- 608 s (P < 0.05, ANOVA), but the increase induced by the enalapril + prazosin combination was significantly greater (P < 0.025, MANOVA) from 214 +/- 271 to 1007 +/- 784 s as was the increase in creatinine clearance (P < 0.05).
 ...
PMID:Concurrent alpha 1 adrenergic blockade and angiotensin converting enzyme inhibition in the treatment of congestive heart failure. 901 70

This study was designed to investigate the possible mechanisms whereby enalapril improves cardiac function and mortality in chronic heart failure. We explored potential mechanisms by following 41 patients with early heart failure over the course of 1 year. These patients were randomized in a prospective triple-blind manner to receive either enalapril or placebo. Over the 1 year, repeated measurements were obtained of echocardiographic parameters, glomerular filtration rate, renal blood flow, hematocrit, plasma neurohormones, and QTc dispersion. Echocardiographic parameters improved with enalapril but deteriorated with placebo (cardiac output 4.6 +/- 1.6 to 3.7 +/- 1.5 L/min with placebo, and 4.5 +/- 1.3 to 5.8 +/- 2.0 L/min with enalapril; p <0.01). In contrast, there were no significant changes in renal blood flow (518 +/- 185 to 509 +/- 180 ml/min/1.73 m2 with placebo, and 541 +/- 142 to 504 +/- 162 ml/min/1.73 m2 with enalapril). Glomerular filtration rate changed from 79 +/- 20 to 78 +/- 19 ml/min/1.73 m2 with placebo, and from 85 +/- 21 to 73 +/- 27 ml/min/1.73 m2 with enalapril (p = 0.051). Enalapril reduced hematocrit (0.414 +/- 0.041 to 0.377 +/- 0.040%) significantly more than placebo (0.420 +/- 0.029 to 0.411 +/- 0.023 l/l; p <0.01). In addition, enalapril produced a marked reduction in QTc dispersion (93 +/- 36 to 88 +/- 28 ms with placebo and 93 +/- 35 to 60 +/- 22 ms with enalapril; p <0.05). Thus, enalapril significantly reduced hematocrit and reduced QTc dispersion in early heart failure. Both of these effects, but especially the latter, could be an important mechanism for the reduced mortality seen with angiotensin-converting enzyme inhibitors in heart failure. In contrast, renal hemodynamics did not parallel either the placebo-induced deterioration in cardiac function or the enalapril-induced improvements in cardiac function.
 ...
PMID:Enalapril reduces QTc dispersion in mild congestive heart failure secondary to coronary artery disease. 941 60

Studies in patients with moderate heart failure have shown a positive relation between atrial size and plasma atrial natriuretic peptide (ANP)(99-126) concentrations; however, the relation of the hormone level and left atrial size and left ventricular function in patients with severe chronic heart failure has not been determined. Fifty-three patients from the Cooperative North Scandinavian Enalapril Survival Study with severe chronic heart failure were evaluated with M-mode echocardiography and determination of plasma concentrations of ANP(99-126). In 35 patients, the plasma level of N-terminal ANP(1-98) was also measured. A significant negative relation was found between ANP(1-98), ANP(99-126), and left atrial diameter (r = -.28, P = .05 and r = -.41, P < .005, respectively). Plasma concentrations of both ANP(1-98) and ANP(99-126) were related to left ventricular systolic function as determined by the systolic time interval index (r = .4, P < .05 and r = .29, P < .05, respectively). A significant improvement of left ventricular systolic function was found in the enalapril group but not in the placebo group. After 6 weeks of therapy, no correlation was found between changes in left atrial size or systolic function or changes in either the ANP(1-98) or ANP(99-126) concentration. The results indicate that high ANP(1-98) or ANP(99-126) plasma concentration is determined by the depressed left ventricular function rather than increased left atrial size in patients with chronic severe heart failure. The findings suggest that the ANP release relation to atrial pressure/atrial size is distorted in severe heart failure.
 ...
PMID:Atrial natriuretic peptide ANP(1-98) and ANP(99-126) in patients with severe chronic congestive heart failure: relation to echocardiographic measurements. A subgroup analysis from the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS). 1283 17

The mechanisms responsible for abnormal fluid retention in congestive heart failure (CHF) are unclear. Studies were conducted to elucidate how endothelin (ET) may contribute to salt and water retention. Cardiomyopathic (CM) hamsters with moderate heart failure were employed for in vivo and in vitro trials. Clearance methods were used to compare the level of renal function in CM hamsters and control animals. Radioligand binding studies were also performed to determine ET receptor distribution in the inner medullary collecting ducts. CM hamsters exhibited an attenuated response to ANF infusion (FENa: 2.7 +/- 0.5 vs. 5.9 +/- 0.8%, p < 0.01; FEH2O: 1.7 +/- 0.3 vs. 3.2 +/- 0.4%, p < 0.01; UcGMP: 11.2 +/- 2.3 vs. 16.6 +/- 2.0 pmol/min, p < 0.05) and a decrease in total ET receptor density (532 +/- 77 vs. 959 +/- 154 fmol/mg protein, p < 0.005). Particularly ETB receptors were significantly reduced (214 +/- 26 vs. 483 +/- 88 fmol/mg protein, p < 0.003). Enalapril therapy simultaneously restored the natriuretic and diuretic effects of ANF and ET receptor density in the diseased animals. These studies suggest that the renin-angiotensin-aldosterone system and ET hormonal system act together, via ETB receptor downregulation, to promote the abnormal fluid retention observed in CHF.
 ...
PMID:Downregulation of endothelin B receptors in cardiomyopathic hamsters. 957 Apr 34


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