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)

For 3 months, we followed up 40 patients with acute myocardial infarction, 20 were randomly assigned to treatment with captopril and 20 to placebo, to elucidate mechanisms inducing left ventricular volume enlargement and development of congestive heart failure. Echocardiographic follow-up could be obtained in 28 patients, 11 of whom showed more than a 10% increase in left ventricular systolic and/or diastolic volumes (captopril n = 3/15, placebo n = 8/13, p = 0.05). Volume increase was significantly associated with an impairment in exercise capacity (VO2 max in patients with vs. without volume enlargement 24.7 +/- 1.7 vs. 29.5 +/- 1.9 ml O2/kg/min; p < 0.05). Plasma renin activity, angiotensin II and catecholamines were normal in the acute and chronic postinfarction phase in patients on placebo as well as in patients 12-24 h after captopril intake. Plasma atrial natriuretic peptide concentration (ANP) was increased immediately after myocardial infarction, but ANP levels almost normalized in patients with captopril treatment, while they continued to be elevated in patients on placebo. The only technical parameter able to predict left ventricular volume increases was the sphericity index (28.7 vs. 35.7; p = 0.07). We concluded that morphologic deformation and filling pressures as estimated from elevated ANP levels are major factors promoting remodelling following myocardial infarction. ACE inhibitors might exert their favorable effect predominantly by reducing filling pressure.
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PMID:Mechanisms involved in cardiac enlargement and congestive heart failure development after acute myocardial infarction. 130 Dec 46

Stabilization of biologically active conformations of native peptides by cyclization or introduction of hindering residues led to peptidominetics endowed with high affinity and selectivity for one class of receptors and able to cross the blood brain barrier. This is the case of BUBU, Tyr-D-Ser(OtBu)-Gly-Phe-Leu-Thr(OtBu) and BUBUC, Tyr-D-Cys-(OtBu)-Gly-Phe-Leu-Thr(OtBu) for the opioid delta receptors and of BC 254, Boc-gamma-D-Glu-Tyr(SO3H)-Nle-D-Lys-Trp-Nle-Asp-PheNH2 and of BC 264, Boc-Tyr(SO3H)gNle-mGly-Trp-MeNle-Asp-PheNH2 for central CCK-B receptors. Inhibition of metabolizing peptidases such as aminopeptidase N and endopeptidase 24.11 (NEP) for enkephalins and of NEP and ACE for atrial natriuretic peptide and angiotensin I by mixed inhibitors such as kelatorphan and RB 101 or ES14, rationally designed by taking into account the structural differences in the active site of these zinc-metallopeptidases, led to potent analgesics devoid of the major morphine side effects or to new antihypertensives.
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PMID:Peptidomimetics as receptors agonists or peptidase inhibitors: a structural approach in the field of enkephalins, ANP and CCK. 132 Apr 19

Two metallopeptidases, angiotensin converting enzyme (ACE) and neutral endopeptidase (NEP) are involved respectively in the release of angiotensin II which is a vasoconstrictor, and in the metabolism of atrial natriuretic peptide which is diuretic and bradykinin which is a vasodilatator. The dual inhibition of these two peptidases represents a new way to regulate the blood pressure in various cardiovascular diseases. Taking into account the mechanism of action of metallopeptidases and the substrate specificity of ACE and NEP, dual inhibitors corresponding to the general formula HS-CH2-CH(R1)CONH-CH(R2)COOH and HS-CH(R1)CONH-CH(R2)CONH-CH(R3)COOH and having inhibitory potencies on each enzyme in the nanomolar range were designed. The most efficient inhibitors have been transformed into lipophilic prodrugs which were found to be active after oral administration. These compounds have been tested on an experimental model of hypertension in rats and, as expected, have been shown to be both diuretic (NEP inhibition) and hypotensive (ACE inhibition).
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PMID:[Dual inhibition of converting enzyme and neutral endopeptidase: a research new way in the field of hypertension]. 133 91

To elucidate the mechanism underlying the sodium retention caused by alpha 1-adrenoceptor blockade in man, a placebo-controlled, randomised, double-blind study has been made of the acute effects of bunazosin an alpha 1-antagonist, on urinary sodium excretion, atrial natriuretic peptide (ANP), arginine vasopressin (AVP), and the renin-aldosterone system in 7 healthy men. A single oral dose of bunazosin 2.0 mg caused a significant reduction (P less than 0.05) in urinary sodium excretion after 0-2 h, 2-4 h, and 4-6 h. The mean values for plasma ANP, AVP, aldosterone, and cortisol concentrations at those times were similar after placebo and bunazosin, and plasma renin activity was significantly increased 2 and 4 h after bunazosin. Pretreatment with oral enalapril 10 mg, an angiotensin converting enzyme inhibitor, did not prevent the bunazosin-induced reduction in urinary sodium excretion. There was a significant positive correlation between the drug-induced changes in blood pressure and urinary sodium excretion. The results suggest that ANP, AVP, and renin-aldosterone may play little role in the sodium retention caused by acute alpha 1-adrenoceptor blockade in man.
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PMID:Acute effect of an alpha 1-adrenoceptor antagonist on urinary sodium excretion, plasma atrial natriuretic peptide, arginine vasopressin, and the renin-aldosterone system in healthy subjects. 135 18

Myocardial pump deficiency is regarded to be the hemodynamic hallmark of congestive heart failure. A decline of arterial pressure in the systemic circulation is counter-regulated by vasoconstriction in the arteriolar vascular bed; the compensatory vasoconstriction, however, results in an increased afterload that in turn aggravates myocardial pump deficiency. As part of the counterregulatory systems the sympathetic nervous system is activated (increase of neuronal activity, increased plasma norepinephrine) and the renin-angiotensin-aldosterone system is stimulated as well (increased plasma renin activity, elevated angiotensin II serum levels, hyperaldosteronism). In parallel, serum levels of antidiuretic hormone (ADH) is despite a serum hypoosmolarity increased and only poorly compensated by release of the atrial natriuretic peptide. On the cellular level, congestive heart failure leads to a shift of the expression of contractile proteins towards to fetal forms (for instance myosin-isoenzymes). Although the counterregulatory activation of the neuroendocrine systems vasoconstricts the peripheral arteries thereby maintaining perfusion of vital organs, the rise in afterload ultimately leads to a progression of congestive heart failure. Consequently, vasodilators (such as ACE-inhibitors) that not only induce vasodilation in the peripheral arteries, but also inhibit progressive neuroendocrine stimulation evolved as excellent compounds for treating congestive heart failure.
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PMID:[Pathophysiology of left heart failure with reference to hemodynamic and neurohumoral changes]. 135 6

Diuretics have long been used to lower blood pressure in hypertensive patients or to control body fluid and electrolyte homeostasis in diseases such as congestive heart failure, chronic renal failure or cirrhosis. The initial response to diuretics is a negative sodium and fluid balance. The diuretic-induced loss of salt and water activates several hormonal systems such as vasopressin, the renin-angiotensin-aldosterone system or the sympathetic nervous system which tend to compensate for the changes in sodium and water balance. This neurohormonal response may have important clinical implications. Thus, the activation of the renin-angiotensin-aldosterone cascade appears to be partially responsible for the flat dose-blood pressure response curve of thiazides in hypertensive patients. It may also be responsible for the difference between responders and non-responders to diuretic therapy and for the development of side-effects such as hypokalaemia, metabolic alkalosis or hyponatraemia. There are several ways to prevent the undesirable consequences of the neurohormonal responses to diuretics. The first is to use low doses of these agents. It is also possible to combine them with agents that block the activity of the renin-angiotensin-aldosterone system such as ACE inhibitors or in combination with drugs that reduce aldosterone secretion such as calcium antagonists. The development of drugs able to enhance urinary sodium excretion and to reduce simultaneously the activity of the renin-angiotensin-aldosterone system may offer a new interesting alternative. This might perhaps be achieved in the future with the administration of neutral endopeptidase inhibitors which interfere with the enzymatic degradation of atrial natriuretic peptide.
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PMID:Neurohormonal consequences of diuretics in different cardiovascular syndromes. 136 43

In the guinea-pig, perindopril inhibited plasma angiotensin converting enzyme (ACE) by 90% when given orally at 2 mg/kg/day during 10 days. Mean blood pressure and plasma aldosterone, cortisol and vasopressin concentrations were not modified by this treatment, while plasma renin activity (PRA) and plasma angiotensin I concentrations increased significantly. The same parameters were studied using a constant intravenous 30 min-infusion of atrial natriuretic peptide (ANP) (0.1 micrograms.kg-1min-1). This dose of ANP infused to anesthetized guinea-pigs induced a significant decrease in mean blood pressure (about -20%) in control and in perindopril treated animals. In ANP infused animals, plasma aldosterone and cortisol concentrations decreased similarly in both groups by about -50%, whereas plasma vasopressin concentrations increased in controls (+169%) but not in perindopril treated guinea-pigs. An increase in PRA and plasma angiotensin I concentrations was observed in both groups after the infusion of ANP. Thus, when ANP demonstrated an potent hypotensive effect a concomitant increase in PRA occurred. The rise observed in vasopressin concentration in control animals was probably mediated by angiotensin II. The fall in plasma aldosterone and cortisol concentrations observed after ANP infusion demonstrated a direct potent action of ANP at the adrenal levels.
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PMID:Cardiovascular and hormonal responses to ANP infusion in the guinea-pig: effects of angiotensin-converting enzyme inhibition with perindopril. 137 87

The relationship between plasma atrial natriuretic peptide (ANP) and plasma renin activity (PRA) was examined in patients with stable chronic obstructive pulmonary disease (COPD, n = 17). The plasma ANP level in patients was approximately twice that in normal subjects. A reciprocal relationship between ANP and PRA was shown in normal subjects; however, this relationship was not observed in COPD. Plasma ANP levels inversely correlated with PaO2, and tended to inversely correlate with angiotensin converting enzyme activity in serum. These results demonstrate that patients with COPD have higher plasma ANP concentration, and that ANP and PRA are not reciprocally related in stable COPD.
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PMID:[Atrial natriuretic peptide and plasma renin activity in patients with stable chronic obstructive pulmonary disease]. 138 34

We measured plasma levels of atrial natriuretic peptide (ANP) in 9 patients of Duchenne muscular dystrophy (DMD) and 3 patients of Becker muscular dystrophy with congestive heart failure (CHF). Administration of digitalis, catecholamine and angiotensin converting enzyme inhibitor resulted in decrease of ANP levels as well as improvement of clinical symptoms of CHF and cardiomegaly. Four DMD patients whose ANP levels were more than 200 pg/ml after the treatment of CHF showed poor prognosis. These results suggest that ANP is a useful marker for the treatment of CHF in progressive muscular dystrophy.
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PMID:[Alteration of atrial natriuretic peptide in progressive muscular dystrophy with congestive heart failure]. 142 36

To test the effect of converting enzyme inhibition (CEI) on diabetes, with or without renal insufficiency, we studied streptozotocin-induced diabetic rats, with or without reduced renal mass, which were treated with insulin in sufficient amounts to maintain glucose values in the mild to moderately hyperglycemic range. We found that diabetes increased glomerular filtration rate (GFR) (inulin clearance, 2.3 +/- 0.5 ml/min vs 1.9 +/- 0.1 ml/min; p < 0.05) and blood pressure (137 +/- 15 mm Hg vs 116 +/- 6 mm Hg; p < 0.05) but did not increase plasma atrial natriuretic peptide (ANP) values, when compared with control rats (72 +/- 38 vs 68 +/- 24 pg/ml). CEI decreased GFR and blood pressure to control values. In rats with diabetes and concomitantly reduced renal mass, hypertension, elevated ANP values, proteinuria, and glomerulosclerosis were prominent features. CEI was associated with reduced blood pressure (172 +/- 17 mm Hg vs 138 +/- 15 mm Hg; p < 0.05), without a concomitant decrease in GFR (1.1 +/- 0.1 ml/min vs 1.1 +/- 0.1 ml/min). Further, CEI reduced the elevated ANP values (140 +/- 34 pg/ml vs 66 +/- 19 pg/ml; p < 0.05) to those of control rats. CEI reduced proteinuria by 50% and ameliorated the histopathologic changes. In separate experiments, rats with 5/6th nephrectomy and hypertension but without diabetes were also found to have elevated ANP levels that decreased to control values with CEI. The data speak for a renal protective effect of angiotensin I-converting enzyme inhibition in this model but do not support a specific role for ANP in the model of diabetes with concomitantly reduced renal mass.
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PMID:Effects of angiotensin-converting enzyme inhibition in diabetic rats with reduced renal function. 145 98


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