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

The acute systemic and regional hemodynamic responses to a single oral dose (4 mg) of the angiotensin converting enzyme inhibitor perindopril were investigated in 10 patients with severe congestive heart failure. Perindopril produced significant and long-lasting decreases in systemic vascular resistance (-18%), right atrial pressure (-60%), and mean pulmonary capillary wedge pressure (-28%), whereas it significantly increased cardiac index (+ 12%). Brachial (+ 130%, pulsed Doppler technique) and renal (+ 34%) blood flows were also significantly increased whereas hepatic blood flow remained unchanged. Brachial flow/cardiac output and renal flow/cardiac output ratios increased significantly from 0.8 to 1.6 and from 13.2 to 16.5, respectively. The maximal decreases in forearm and renal (but not in systemic) vascular resistances were correlated with the basal plasma norepinephrine concentrations but not plasma epinephrine concentrations or plasma renin activity. We conclude that in severe heart failure (a) perindopril considerably improves systemic hemodynamics and exerts an inhomogeneous vasodilating effect, resulting in a redistribution of flows toward the forearm and renal territories, (b) norepinephrine is a major determinant of the arteriolar tone in these two vascular beds, and (c) the pulsed Doppler is a particularly suitable method to non-invasively detect and assess hemodynamic improvements in heart failure patients.
J Cardiovasc Pharmacol 1990 Apr
PMID:Systemic and regional hemodynamic effects of perindopril in congestive heart failure. 169 80

The therapeutic potential of atrial natriuretic peptide (ANP) was assessed in an ovine model of heart failure induced by rapid left ventricular (LV) pacing and compared with the effects of angiotensin converting enzyme (ACE) inhibition. Hemodynamic, hormonal, and metabolic measurements were studied during three 5-day periods of LV pacing. No treatment (control) or a continuous ANP infusion (25 ng/kg/min) was given in random order during the first two periods, while ACE inhibitor was always given during the third period. Baseline measurements immediately prior to the start of each pacing phase showed no significant variation. Significant neurohumoral activation and hemodynamic responses were observed in each pacing phase. During ANP infusion, plasma ANP levels were 3-5-fold higher than those observed in the control or ACE inhibition treatment phases. Compared with control, a natriuresis was observed on the first day, whereas glomerular filtration rate (GFR) tended to be maintained during ANP infusion. The rise in left atrial pressure and plasma aldosterone tended to be blunted. When the two treatment phases were compared, the rise in left atrial pressure during LV pacing was less with ACE inhibition, whereas there was a similar reduction in sodium retention after the initial natriuresis with ANP. By contrast, GFR tended to be maintained better during ANP infusion compared to ACE inhibition. These results suggest that ANP, or a similar "enhancing" analogue, may be useful in the treatment of heart failure, especially if administered early in the development of the disorder.
J Cardiovasc Pharmacol 1990 Apr
PMID:ANP infusion in the treatment of heart failure and comparison with ACE inhibition. 169 81

The hypotensive effects of three different angiotensin converting enzyme (ACE) inhibitors (captopril, enalapril, and lisinopril) and two angiotensin II (AII) analogues ([Sar1Ile5Ala8]AII and [Sar1Ile5Thr8]AII) were compared in conscious, freely-moving Brattleboro rats after 14 h of water deprivation. There was no difference between the hypotensive effects of the three ACE inhibitors. Neither was there any difference between the hypotensive effects of the two AII antagonists, although when administered following ACE inhibition, [Sar1Ile5Thr8]AII caused a transient pressor effect that was significantly less than that caused by [Sar1Ile5Ala8]AII. ACE inhibition caused a greater fall in blood pressure (BP) than AII antagonism and caused an additional fall in BP during AII antagonism. These results indicate an additional hypotensive effect of ACE inhibitors, over that of AII antagonists, that is not readily accounted for in terms of nonspecific effects of the former or agonistic properties of the latter.
J Cardiovasc Pharmacol 1990 Apr
PMID:Hypotensive effects of angiotensin II analogues and angiotensin converting enzyme inhibitors in water-deprived Brattleboro rats. 169 84

In recent years, the role of the renin-angiotensin system (RAS) in the development of hypertension has been investigated extensively. Studies have shown that there are actually two systems: a tissue and a circulating RAS. The control of hypertension is focused primarily in the RAS in the cardiovascular system and the brain. By manipulating the RAS with angiotensin converting enzyme (ACE) inhibitors, researchers have learned that the cardiovascular neuronal centers in the brain have receptor sites for the actions of angiotensin II (Ang II). Receptors for Ang II are found in the medulla oblongata in neurons involved in the regulation of baroceptor activity. Since studies in both animals and hypertensive patients indicate that ACE inhibitors reduced sympathetic activity and enhanced baroceptor sensitivity, it is possible that the primary hypotensive mechanism of these agents is through blockage of Ang II formation in the cardiovascular centers of the brain.
J Cardiovasc Pharmacol 1990
PMID:The renin-angiotensin system: importance in physiology and pathology. 169 11

Recent studies in animal models suggest that glomerular capillary hyperperfusion and hypertension, rather than ischemia, cause renal injury. Interventions that control glomerular capillary hypertension may protect against progressive injury, even in the presence of continued systemic hypertension. In the absence of systemic hypertension, diabetes mellitus is a prominent clinical example of glomerular hypertension. Animal studies have shown that glomerular hemodynamic abnormalities, especially elevations in glomerular pressure, play an important role in the pathogenesis of diabetic glomerulopathy. A number of clinical observations suggest that angiotensin converting enzyme (ACE) inhibitors may delay the progression of diabetic nephropathy by their effects on renal hemodynamics. In experimental animals, comparisons between calcium channel blockers and ACE inhibitors have shown the latter to be more effective in protecting the kidneys. Preliminary clinical studies indicate that ACE inhibitors may have advantages in preserving renal function in hypertensive and diabetic patients with renal failure.
J Cardiovasc Pharmacol 1990
PMID:Renal effects of converting enzyme inhibitors in hypertension and diabetes. 169 12

There have been many changes in the treatment of hypertension over the past few decades. The Joint National Committee on the Detection, Evaluation, and Treatment of High Blood Pressure (JNC) has published four reports since 1977. The first three highlighted diuretic therapy as the main ingredient of stepped care for hypertensive patients. In the fourth report, this position has been revised to a patient-oriented, or individualized, approach. The shift reflects the results of many studies on hypertensive patients treated with a variety of approaches and drugs, including diuretics, beta-blockers, angiotensin converting enzyme (ACE) inhibitors, sympatholytics, and calcium channel blockers. After analyzing the patient's history, physical, and laboratory findings, the report recommends making choices from the various agents, based on patient demographics, sequelae, concomitant diseases, and other risk factors such as cholesterol levels.
J Cardiovasc Pharmacol 1990
PMID:JNC-IV and the evolution of stepped care to individualized treatment of hypertension. 169 13

Patient compliance is crucial to successful medical treatment. Many factors contribute to compliance, including age, sex, other sociodemographic factors, finances, intelligence, complexity of therapeutic regimen, and patient-physician rapport. Compliance is especially critical in medical conditions requiring prolonged therapy, such as hypertension. Historically, compliance among hypertensive patients has been alarmingly poor, with a 50% drop-off after 1 year and fewer than 20% still in therapy after 5 years. The use of enalapril, the long-acting angiotensin converting enzyme (ACE) inhibitor that allows for a once-daily regimen, has improved treatment success and compliance. This probably is due to the efficacy of the drug, coupled with a low incidence of side effects.
J Cardiovasc Pharmacol 1990
PMID:Patient compliance and angiotensin converting enzyme inhibitors in hypertension. 169 14

Congestive heart failure (CHF) is a complex clinical syndrome affecting 1% of the U.S. population. The basic dysfunction, a lack of sufficient blood flow to the periphery, triggers reflex neurohumoral mechanisms that cause systemic vasoconstriction and sodium and water retention as the body attempts to protect vital organs. This, in turn, results in additional work for the failing heart and further deterioration. Vasodilators, in general, and angiotensin converting enzyme (ACE) inhibitors, in particular, interrupt this pathophysiology and improve hemodynamics. Enalapril, a long-acting ACE inhibitor, has been demonstrated to improve New York Heart Association (NYHA) functional class, pulmonary capillary wedge pressure, cardiac index, maximum oxygen uptake, and exercise tolerance in CHF patients. Data from a recent trial provide evidence that a group of patients with severe CHF who were treated with enalapril showed reduced heart size, reduced need for other heart-failure medication, and reduced mortality.
J Cardiovasc Pharmacol 1990
PMID:Enalapril in the treatment of congestive heart failure. 169 16

Hypertension is one of the primary risk factors for cardiovascular disease, especially coronary artery disease (CAD), cerebrovascular disease, and congestive heart failure. Recent analysis of the numerous prospective clinical trials of the efficacy of antihypertensive therapy performed during the past quarter century has shown that active treatment reduces mortality and cerebrovascular disease but has not prevented CAD. The reason for this paradox--that lowering blood pressure does not reduce CAD mortality or morbidity--is uncertain. During the past several years, it has become clear that hyperinsulinemia and peripheral insulin resistance constitute the link between hypertension, obesity, and non-insulin-dependent diabetes mellitus, three conditions in which the rate of CAD is very high. Other studies have shown that hyperinsulinemia is a potent cardiovascular risk factor. Epidemiologic surveys and retrospective reviews of clinical experience have pointed out the surprising fact that when hypertension and non-insulin-dependent diabetes mellitus occur in the same patient, hypertension is likely to be diagnosed first and the risk of developing diabetes is much higher if antihypertensive drugs (thiazide diuretics or beta-adrenoreceptor blockers) were given. Recently, careful studies have shown that both thiazide diuretic and beta-adrenoreceptor blockers worsen insulin sensitivity, whereas angiotensin converting enzyme inhibitors (captopril) and peripheral alpha 1-blockers (prazosin) improve it and also favorably affect the levels of other atherogenic risk factors. Although it is too early to be certain, this information suggests that, pending the results of long-term clinical trials that measure clinical events, treatment of hypertension might be better able to reduce CAD if it were directed at improving insulin sensitivity. Nonpharmacologic measures that reduce hyperinsulinemia, weight loss, and exercise should be vigorously recommended, and pharmacologic therapy should be aimed at avoiding drugs that worsen insulin sensitivity, as long as blood pressure is successfully reduced.
J Cardiovasc Pharmacol 1990
PMID:The coronary artery disease paradox: the role of hyperinsulinemia and insulin resistance and implications for therapy. 169 28

In a recent study in which metabolic characteristics of newly detected obese and nonobese hypertensive subjects were compared with those of normotensive subjects, insulin sensitivity was decreased, fasting insulin values and insulin values after an intravenous glucose tolerance test (IVGTT) were increased, and fasting and IVGTT glucose values were increased in both hypertensive groups. Furthermore, adverse alterations in lipid profile variables were found in the hypertensive groups when compared with the normotensive group. The effects of various antihypertensive agents on these metabolic variables have been assessed in prospective trials. Treatment with the beta 1-selective blocking agents metoprolol and atenolol was associated with decreased insulin sensitivity and increased fasting values of insulin and glucose. There were also indications of a suppressive effect on insulin secretion during IVGTT, as well as an increase in serum triglycerides and a decrease in serum high-density lipoprotein cholesterol. Hydrochlorothiazide treatment was associated with a decrease in insulin sensitivity and an increase in blood glucose concentrations. In addition, hydrochlorothiazide increased total cholesterol, particularly the low-density lipoprotein fraction. The calcium channel blocker diltiazem did not appear to produce any negative metabolic effects. Treatment with the angiotensin converting enzyme inhibitor captopril resulted in increased insulin sensitivity with no adverse effects on lipids. All of the agents reduced blood pressure to a similar degree. These findings, and those of other studies, suggest that captopril and diltiazem offer advantages over the other agents with regard to effects on risk factors for coronary artery disease other than hypertension. Unlike diltiazem, captopril improves insulin sensitivity and this may prove to be important.
J Cardiovasc Pharmacol 1990
PMID:Insulin sensitivity in newly detected hypertensive patients: influence of captopril and other antihypertensive agents on insulin sensitivity and related biological parameters. 169 31


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