Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.15.1 (ACE)
 18,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Primary hypertension is associated with a lack in renal kallikrein activity which might be one of the reasons for the blood pressure elevation. Some smaller and partially uncontrolled studies suggested that an oral substitution of glandular kallikrein lowers blood pressure by a kinin-mediated vasodilation and increased natriuresis. To test this hypothesis we treated in two studies over 100 patients with untreated mild to moderate primary hypertension (WHO I-II) for 5 resp. 12 weeks in a double blind randomized and placebo controlled manner with 1800 U glandular kallikrein orally. Blood pressure measurements were performed according to the two study designs after 3 and 5 resp. 8 and 12 weeks of treatment sphymomanometrically in the day time course. No significant changes in blood pressure by kallikrein treatment could be observed at any time. Neither renal kallikrein excretion, renin and ACE-activity nor blood glucose concentration in diabetics or non-diabetics was changed. Thus, we could undoubtedly demonstrate that oral applied glandular kallikrein has no effect on primary hypertension.
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PMID:Lack of oral kallikrein in lowering systemic blood pressure in primary hypertension. 146 64

Serum lipids of 80 patients with moderately severe essential hypertension under four different antihypertensive therapies were compared to ten matched hypertensives on a placebo, after eight weeks of therapy. The results in the serum lipid parameters measured after therapy showed with enalapril a significant increase in high-density lipoprotein cholesterol (HDL-C) and a decrease in the total cholesterol/HDL-C ratio. With benazepril a significant decrease in the total cholesterol/HDL-C ratio was obtained. With the diuretic combination Epitens the effect on serum sodium and potassium was minimal. No significant changes were found in the lipoprotein profile following the administration of the placebo. Both angiotensin converting enzyme inhibitors (enalapril and benazapril) induced a significant improvement in the atherogenic ratio; as well as the calcium antagonist (isradipine), though to a less extent. The diuretic Epitens induced an insignificant deterioration of the atherogenic ratio.
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PMID:Serum lipoprotein profile under different antihypertensive therapy. 147 76

Today, essential hypertension is considered to be genetically closely related to disordered peripheral glucose metabolism, and this situation is described by the term metabolic syndrome. Both diseases--hypertension and type II diabetes--submit the heart and arterial vessels to an unphysiological, chronic stress, which they can compensate only for a certain time. Today, when antihypertensive treatment is indicated, drugs capable of preventing late vascular injury while at the same time having the potency to reverse already existing organic changes, are employed. ACE-inhibitors are presently considered to be the most potent substances that are capable of exerting a positive effect on hypertension-associated changes, while not increasing the individual risk profile in the development of arteriosclerosis. The present paper discusses the new ACE-inhibitor, cilazapril, which can be administered in a practical single dose and develops a profile of action typical of ACE-inhibitors in hypertensives with and without an accompanying metabolic syndrome.
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PMID:[ACE inhibition with cilazapril. Major therapeutic aspects: hypertension and metabolic syndrome]. 147

As the major regulator of arterial blood pressure and sodium balance, the renin axis supports normotension or hypertension via angiotensin-mediated vasoconstriction and angiotensin plus aldosterone-induced renal sodium retention. In this endocrine servo control, renal renin is released by hypotension or salt depletion; conversely, with hypertension or volume excess, plasma renin activity falls to zero. Accordingly, any renal renin secretion is abnormal in the face of arterial hypertension. Human hypertensive disorders comprise a spectrum of abnormal vasoconstriction-volume products (renin-sodium profiles). Excess plasma renin activity for the sodium balance is created by nephron heterogeneity in which a subpopulation of ischemic nephrons hypersecretes renin and retains sodium. This excess renin impairs adaptive natriuresis of neighboring normal nephrons. Research defining the pivotal role of vascular cytosolic calcium for transducing sodium or renin-mediated vasoconstriction explains the selective value of calcium antagonists for correcting the sodium-volume-mediated, and beta-blockers or angiotensin converting enzyme inhibitors for correcting renin-mediated, arteriolar vasoconstriction. The renin precursor prorenin appears to be physiologically active, causing selective vasodilation that offsets renin-mediated vasoconstriction. Overactivity of prorenin may be involved in the hyperperfusion vascular injuries of diabetes mellitus and toxemias. Prorenin underactivity may facilitate renin-mediated ischemic vascular injury. In essential hypertension, undue plasma renin activity is powerfully and independently associated with heart attack risk. Conversely, patients with low renin activity are protected from heart attack despite higher blood pressures and greater age. Also, renin or angiotensin administration consistently causes vascular injury in the heart, brain, and kidneys of animals. These data suggest new potentials for the prevention of cardiovascular sequelae (heart attack and stroke) by using explicit strategies to curtail plasma renin activity.
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PMID:Lewis K. Dahl Memorial Lecture. The renin system and four lines fo hypertension research. Nephron heterogeneity, the calcium connection, the prorenin vasodilator limb, and plasma renin and heart attack. 151 45

Numerous pharmacologic agents are capable of lowering the blood pressure of hypertensive patients; however, each drug has a characteristic side effect profile and effect on cardiac performance. In this study, the hemodynamic effects of the angiotensin converting enzyme inhibitor fosinopril were assessed at rest and at peak upright bicycle exercise by first-pass radionuclide cineangiography in 12 patients with essential hypertension. Fosinopril reduced blood pressure at rest in the seated position from 152/101 to 131/85 mm Hg (P less than .01) and at peak exercise from 206/103 to 184/91 mm Hg (P less than .01). Fosinopril therapy was associated with an increase in stroke volume and cardiac output and a decrease in systemic vascular resistance at rest and during peak exercise. Both peak ejection rate and peak filling rate increased significantly at rest during fosinopril therapy. The unique cardiotropic response to fosinopril may reflect its effects on the myocardial renin-angiotensin system, and suggests that this agent may offer a therapeutic advantage compared with other angiotensin converting enzyme inhibitors.
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PMID:Effects of fosinopril on cardiac function in patients with hypertension. Radionuclide assessment of left ventricular systolic and diastolic performance. 153 64

Diastolic dysfunction is often present in patients with arterial hypertension. It is not only the consequence of an increased left ventricular muscle mass but also due to a progressive fibrosis of the cardiac interstitium. Experimental studies have shown a close relationship between the degree of interstitial cardiac fibrosis and the activity of the renin-angiotensin system (RAS). Reversal of collagen deposition can be induced by inhibition of the RAS. The purpose of this study was to evaluate the therapeutic potential of ACE inhibitors not only in lowering blood pressure in patients with essential hypertension, but also in normalizing an impaired diastolic filling pattern in the left ventricle. Monotherapy with a single dose of 2.5-5 mg Cilazapril for a period of 6 months was effective in reducing mean arterial blood pressure by about 10 mmHg over the entire 24-h interval. The main reduction occurred throughout the day, but lower blood pressure values during the night were hardly affected at all. The pre- and post-treatment values of the 24-h blood pressure were subjected to a modified Fourier analysis, which did not reveal any disturbances in the circadian blood pressure rhythm by the ACE inhibitor. Left ventricular mass, as calculated from echocardiographic measurements, was reduced by 30% after 6 months of treatment. The degree of regression of LV hypertrophy was closely related to the drug-induced fall in mean arterial pressure. The abnormal left ventricular filling pattern before treatment with a predominance of the late diastolic filling period was corrected by 6 months of ACE inhibitor treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Reparative effects of ACE inhibitors on the heart]. 153 2

Perindopril is a non-sulphydryl angiotensin converting enzyme (ACE) inhibitor which requires hydrolysis to its active metabolite, perindoprilat, to produce its effects. Ten cirrhotic patients with mild to severe disease were studied after oral administration of a single 8 mg dose of perindopril as its tert-butylamine salt. Compared with a historical control group of young healthy volunteers receiving the same single oral dose of perindopril, mean AUC values of the prodrug perindopril were double in patients with liver cirrhosis (602 +/- 294 s.d. ng ml-1 h vs 266 +/- 70 s.d. ng ml-1 h) whereas the mean AUC of perindoprilat was found to be similar (134 +/- 139 ng ml-1 h vs 120 +/- 29 ng ml-1 h). The partial metabolic clearance of perindopril to perindoprilat was much lower in the cirrhotics (26 +/- 12 ml min-1 vs 58 +/- 22 ml min-1). The maximum inhibition of plasma ACE activity measured in the cirrhotic patients (87.5 +/- 5.1%) was comparable with that previously reported with perindopril in patients with mild hepatic impairment as well as in patients with essential hypertension. We suggest that liver cirrhosis may be associated with imparied deesterification of perindopril to its active metabolite perindoprilat but that no dosage adjustment of perindopril is required in cirrhotic patients.
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PMID:The pharmacokinetics of perindopril in patients with liver cirrhosis. 157 57

Essential hypertension is a complex clinical disorder in which multiple environmental and genetic factors interact to increase blood pressure. To search for chromosome regions that contain genes regulating blood pressure, some investigators have begun to conduct linkage studies in rodent models of spontaneous hypertension. Preliminary results suggest that in the rat, blood pressure regulatory genes may be located in the vicinity of the kallikrein gene family on chromosome 1, the gene for angiotensin converting enzyme on chromosome 10, the renin gene on chromosome 13, and the major histocompatibility complex on chromosome 20. Some studies have also suggested that blood pressure regulatory loci may be located on the sex chromosomes. Although comparisons between humans and animals should be made with caution, it is hoped that the identification of genes regulating blood pressure in the rat might shed light on the pathogenesis of hypertension in humans.
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PMID:Genetic approaches to hypertension. 161 May 44

OBJECT OF TREATMENT: Antihypertensive treatment in hypertensive patients with insulin-dependent diabetes mellitus is intended to prevent long-term complications, particularly diabetic nephropathy. DIABETIC HYPERTENSIVES WITH ABNORMAL ALBUMINURIA: Antihypertensive therapy, particularly with angiotensin converting enzyme (ACE) inhibitors, typically produces a permanent reduction in the decline of the glomerular filtration rate (GFR) in diabetic patients with abnormal albuminuria. The rate of decline in the GFR during antihypertensive treatment is a well accepted end-point in diabetic renal disease. DIABETIC HYPERTENSIVES WITHOUT ABNORMAL ALBUMINURIA: In insulin-dependent diabetic patients with essential hypertension but with normal urinary albumin excretion there is no reduction in the GFR. Longitudinal studies have shown a fall in the GFR only in the presence of significantly increased urinary albumin excretion. ABNORMAL ALBUMINURIA AS A MARKER OF INCIPIENT NEPHROPATHY: Micro-albuminuria and proteinuria may be pathogenetic factors in the development of nephropathy, leading eventually to end-stage renal failure in diabetic patients. Measurements of micro-albuminuria and proteinuria, in addition to blood pressure recordings, might therefore be used as indications for initiating antihypertensive treatment. NEED TO MONITOR PATIENTS FOR ABNORMAL ALBUMINURIA: Transglomerular macromolecular traffic may produce mesangial damage, with subsequent glomerulopathy and diabetic nephropathy. Thus, close monitoring for micro-albuminuria and proteinuria is desirable in the management of diabetic hypertensive patients.
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PMID:Micro-albuminuria and the organ-damage concept in antihypertensive therapy for patients with insulin-dependent diabetes mellitus. 161 2

The authors investigated in ten patients with essential hypertension changes in the membrane transport of sodium in red blood cells and the intracellular calcium content of thrombocytes during the control period during treatment of hypertension with central sympatholytics and after three-week treatment with an inhibitor of the angiotensin converting enzyme (ACE), enalapril. The effect of enalapril in hypertonic patients was manifested by a rise of the renin plasma activity and the potassium concentration and a reduction of the sodium plasma concentration which corresponds to the inhibition of angiotensin II. The intracellular calcium and sodium content was unaltered. In 8 of 10 patients after enalapril treatment increased values of Vmax for Na(+)-K+ cotransport occurred, incl. 6 patients where at the same time a rise of Vmax Na(+)-Li+ countertransport was recorded.
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PMID:[Membrane transport of cations in erythrocytes during treatment of essential hypertension with angiotensin-converting enzyme inhibitors]. 163 92


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