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: EC:3.4.15.1 (ACE)
18,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The heart is one of the major target organs that becomes secondarily involved with the unrelenting and progressive vascular disease of essential hypertension. As a result of this increasing afterload that is imposed upon the left ventricle, the ventricular chamber adapts structurally and functionally. Structural changes involve an increase in muscle mass that is achieved through left ventricular hypertrophy (in a manner similar to the arteriolar changes demonstrated by increased thickening). Unless antihypertensive therapy is interdicted in this disease process, left ventricular failure will ensue as the major cardiac hemodynamic consequence. Left ventricular hypertrophy is also associated with a risk that is independent of the pressure overload and hemodynamic risk. Although antihypertensive therapy will reduce from the hemodynamic alterations, only recently have epidemiological findings suggested that the independent risk of LVH may be reduced with pharmacological therapy. There are no data available to indicate just which agents may reduce the risk from LVH; but relatively recent studies seem to indicate that while all agents may reduce LVH with prolonged therapy only certain classes of agents will do so independent of their hemodynamic factors. Some of these agents, however, may impair cardiac function if arterial pressure is increased abruptly following therapeutic reduction of cardiac mass. Other agents may preserve normal function--or even may improve function. Among those classes of antihypertensive agents that reduce cardiac mass at least in part due to nonhemodynamic factors, are the angiotensin converting enzyme inhibitors, the calcium antagonists, and most adrenergic inhibitors. Evidence will be presented demonstrating the hemodynamic/structural dissociation of those pharmacological agents that reduce cardiac mass with short-term treatment in spontaneously hypertensive rats with left ventricular hypertrophy. Although centrally active adrenolytic, angiotensin converting enzyme (ACE) inhibitors, and calcium antagonists all reduce cardiac mass, their structural and cardiac functional effects differ greatly. Even within the ACE inhibitor group their effects vary--improving, impairing, or not changing the Frank-Starling relationships following reduction in left ventricular mass. We postulate great variability of cardiac intramyocytic penetrance of the pharmacological agents and their local intracellular effects on mitogenesis of the ventricular myocyte. The implications on cardiac function and therapy have vast potential. Therefore, current investigative areas involving new concepts of molecular biology of the cardiac myocyte may provide great promise to the quest of unraveling some of the newly postulated questions: What is the role of ionized intracellular calcium? Do the local renin-angiotensin systems in the cardiac and vascular myocyte participate in the development and regression of hypertrophy?(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Left ventricular hypertrophy: dissociation of structural and functional effects by therapy. 183 47

The effects of monotherapy with the angiotensin converting enzyme inhibitor benazepril (10 mg once daily) on cardiovascular baroreceptor reflexes were determined in 10 patients with essential hypertension using a randomized, double-blind, placebo-controlled, cross-over protocol. Early sino-aortic baroreceptor/heart rate reflex resetting was apparent with acute treatment; this effect persisted throughout the active treatment period. Changes in baroreflex sensitivity did not appear to mediate the hypotensive effect of benazepril.
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PMID:Effects of the angiotensin converting enzyme inhibitor, benazepril, on the sino-aortic baroreceptor heart rate reflex. 188 95

Vasoactive hormones acting as endocrine, neuroendocrine, or local hormonal systems (intracrine, autocrine, and paracrine) are an important component of the many factors that regulate blood pressure. Hypertension may be the result of an alteration in the balance between vasodepressor and vasopressor hormonal systems. Changes in this balance could be due to genetic factors such as mutations in one of the genes of the vasoactive system or environmental factors that alter the synthesis and release of one or more vasoactive hormones. Endocrine and neuroendocrine vasopressor hormonal systems, such as the renin-angiotensin system and catecholamines, play a well-established and important role in the regulation of blood pressure and the pathogenesis of some secondary forms of hypertension. The blockade of such systems has already resulted in effective antihypertensive treatment. The role of local hormonal systems is less well established; however, recent evidence suggests they also play an important role in the regulation of blood pressure and the pathogenesis of hypertension. Some vasopressor hormonal systems, such as the renin-angiotensin system, can act as both endocrine or local hormonal systems. Work using transgenic rats harboring the mouse Ren-2 gene has conclusively demonstrated that the renin-angiotensin system, acting as a local hormonal system, has the capability to cause severe hypertension. Whether this model of experimental hypertension mimics any type of human hypertension is not known. Vasodepressor hormones such as kinins, prostaglandins, and endothelium-derived relaxing factor (EDRF) act mainly as local hormonal systems, with the notable exception of atrial natriuretic factor, which may act as both an endocrine and a local hormone. The tissue kallikrein-kinin system, acting either directly or via paracrine eicosanoids or EDRF, participates in local regulation of the circulation, renal function, and the acute antihypertensive effect of angiotensin converting enzyme inhibitors. A restriction fragment length polymorphism (RFLP) that distinguishes the kallikrein gene family of a strain of spontaneously hypertensive rats (SHR) from normotensive Brown Norway rats has been identified. In a set of 32 recombinant inbred strains derived from these SHR and Brown Norway strains, the RFLP marking the kallikrein gene family of SHR cosegregated with an increase in blood pressure. Also, in a study of Utah families it was found that a dominant-allele kallikrein gene expressed as high urinary kallikrein excretion was associated with a decreased risk of essential hypertension. In conclusion, vasopressor and vasodepressor hormones, acting not only as endocrine but also as local hormones, play an important role in the regulation of blood pressure and the pathogenesis of hypertension.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Local hormonal factors (intracrine, autocrine, and paracrine) in hypertension. 188 59

The discovery and clinical availability of ACE inhibitor drugs is a triumph of rational drug development and a land-mark in biochemical pharmacology and hypertension research. The clinical pharmacological properties and haemodynamics of the clinically available drugs, captopril and enalapril, are reviewed, as is their therapeutic efficacy in African patients with essential and renal hypertension and chronic congestive heart failure. ACE inhibitors act as balanced arteriolar vasodilators and venular dilators and do not excite a reflex tachycardia in contrast to other vasodilator drugs. Their efficacy is, at least in part, dependent on plasma renin activity, which is low in Blacks and in Africans. Consistent with this, is the poor response to ACE inhibitor monotherapy of essential hypertension in controlled studies in Africans. However, the compensatory neuroendocrine activation which occurs in malignant hypertension, renal failure and congestive heart failure and concurrent diuretic therapy appears to enhance the clinical response to ACE inhibitors in African patients.
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PMID:Angiotensin converting enzyme inhibitors in cardiovascular and renal disease in Africans: a review. 190 20

There is much circumstancial and some direct evidence in humans to suggest that a high consumption of salt predisposes communities and individuals to the development of essential hypertension. Restriction of salt intake in the diet lowers blood pressure in many subjects with high blood pressure and this fall in blood pressure is mediated in part by a diminished renin response to sodium restriction as hypertension develops. The effect of sodium restriction, like diuretics, is additive to many blood pressure lowering drugs, particularly those that inhibit the renin system such as beta-blockers and angiotensin converting enzyme inhibitors.
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PMID:Dietary salt intake and hypertension. 192 Dec 46

Seventeen essential hypertensive patients with normal renal function were treated with a new non-sulphydryl orally active angiotensin converting enzyme (ACE) inhibitor, benazepril, 10 mg given once or twice daily, according to diastolic blood pressure levels, for 6 weeks. In all patients, changes in blood pressure, systemic and renal hemodynamics, plasma renin activity and urinary aldosterone and albumin excretions were assessed at the end of a 2-week placebo run-in period and at the end of the study. Benazepril monotherapy controlled blood pressure well. No changes in cardiac output, heart rate or stroke volume were observed, while peripheral vascular resistance was significantly decreased (-11%, P less than 0.05). Plasma volume was unaltered. The glomerular filtration rate was stable, but effective renal plasma flow was increased because of the marked reduction in renal vascular resistance (-35%) and, therefore, the filtration fraction was decreased. Urinary albumin excretion remained unchanged. A significant increase in plasma renin activity (P less than 0.001) and a decrease in urinary aldosterone excretion were seen. No side effects were observed during the treatment period. In conclusion, our results suggest that benazepril alone is an effective antihypertensive agent in patients with essential hypertension. The blood pressure lowering effect is due mainly to systemic vasodilation and is observed up to 24 h after administration of the drug. The vasodilation appears to be more consistent in the renal than in the systemic circulation.
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PMID:Systemic and renal effects of a new angiotensin converting enzyme inhibitor, benazepril, in essential hypertension. 196 90

The effects of various antihypertensive treatments on the echocardiographic and electrocardiographic findings of left ventricular (LV) hypertrophy were studied in 75 patients with essential hypertension. The hemodynamic effects of the therapy during exercise were also compared. LV mass by echocardiogram was significantly reduced by beta-blockade and angiotensin converting enzyme inhibition (ACEI), but only slightly reduced by Ca channel blockade. QRS high voltage criteria of LV hypertrophy by electrocardiogram were reduced by all 3 of these antihypertensive treatments. At submaximal exercise, the pressor responses were attenuated by captopril, but not influenced by metoprolol or nifedipine. The increase in plasma norepinephrine by exercise was significantly suppressed after captopril, but was somewhat augmented after metoprolol or nifedipine. These observations indicate that the responses of hemodynamics and sympathetic nervous activity to exercise are different after the treatment by beta-blocker, Ca channel blocker or ACEI, in spite of the equal antihypertensive effect. However, it is suggested that the regression of LV hypertrophy might be induced by antihypertensive therapy, though the different grade by the individual drug.
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PMID:Regression of left ventricular hypertrophy in hypertensive patients: responses to exercise by antihypertensive treatment. 197 37

The Captopril Prevention Project (CAPPP) is a prospective, randomized, multi-centre intervention trial designed to investigate whether antihypertensive treatment with the angiotensin converting enzyme (ACE) inhibitor captopril may reduce cardiovascular mortality and morbidity more than a therapeutic regimen which does not include an ACE inhibitor. Secondary objectives are to compare total mortality, the development or deterioration of ischaemic heart disease, left ventricular failure, atrial fibrillation, diabetes mellitus and possible differences in renal function in the two groups. Male and female patients with essential hypertension, aged 25-66 years, will be randomly allocated to antihypertensive treatment which will comprise either the use of the ACE inhibitor captopril or will exclude all types of ACE inhibitors. Some 275 hypertension centres and health care centres in Sweden and Finland will take part in this multi-centre trial. A total of 7000 patients will be recruited and studied for an average period of 5 years, the assumption being that a 20% difference in cardiovascular mortality between the two groups can be detected with a power of 80% at the 5% significance level (two-sided test).
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PMID:The Captopril Prevention Project: a prospective intervention trial of angiotensin converting enzyme inhibition in the treatment of hypertension. The CAPPP Group. 198 Dec 18

The metabolic changes which accompany hyperglycemia in a person with diabetes are thought to cause renal hyperperfusion and intraglomerular hypertension, especially in the person with a predisposition to essential hypertension. Intraglomerular hypertension causing deposition of protein in the mesangium leads to glomerulosclerosis and renal failure. Screening for microalbuminuria can predict which type I diabetic patients will develop nephropathy. The decline in renal function in established diabetic nephropathy can be slowed with aggressive treatment of hypertension. The use of ACE inhibitors may also decrease intraglomerular hypertension. Whether similar treatment in the person with preclinical diabetic nephropathy would delay or prevent the onset of diabetic nephropathy is being investigated. Restricted protein intake, anti-platelet and rheolitic drugs may have a role in the treatment of established diabetic nephropathy. In end stage renal failure, renal transplantation is the treatment of choice. When transplantation cannot be performed, chronic ambulatory peritoneal dialysis is preferable to hemodialysis.
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PMID:Diabetic nephropathy: changing concepts of pathogenesis and treatment. 200 Aug 93

Inhibitors of angiotensin converting enzyme, renin, and the angiotensin II (Ang II) receptor lower the blood pressure of spontaneously hypertensive rats (SHR) used as a model of essential hypertension. Since their plasma renin levels were normal or subnormal, renin in the vascular tissue was considered to play a key role in the maintenance of the hypertension. To clarify the source and localization of renin in SHR, antirenin antibodies, the converting enzyme inhibitors delapril, enalapril, and the Ang II receptor antagonist DuP 753 were administered to intact and bilaterally nephrectomized SHR and their normotensive controls. The efficient hypotensive action of the renin antibody indicated that renin of renal origin is a dominant factor. Gradual but complete disappearance of antihypertensive action of these inhibitors of the renin-angiotensin system upon bilateral nephrectomy indicated the importance of membrane-associated renin of the renal origin and angiotensin converting enzyme in the maintenance of the spontaneous hypertension.
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PMID:Roles of renal and vascular renin in spontaneous hypertension and switching of the mechanism upon nephrectomy. Lack of hypotensive effects of inhibition of renin, converting enzyme, and angiotensin II receptor blocker after bilateral nephrectomy. 200 42


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