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)

One-hundred patients suffering from slight-moderate hypertension (53 m, 47 f, aged between 18 and 78, average 49.08) have been studied in order to assess the effectiveness and tolerance of lisinopril ("Zestril", ICI-Pharma), a new ACE inhibitor in a single daily administration at doses of between 10 and 80 mg in relation to pressure values. Monotherapy with Lisinopril proved effective in 84 patients (88.4%), in 74 of whom (7.9%) pressure values were returned to normal. 11 patients (11.6%) did not respond to treatment. In most cases, the result was obtained with a dose of 20 mg in a single administration (32.6%). The incidence of side-effects was limited and in no case required the withdrawal of the drug.
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PMID:[Multicenter clinical study of the antihypertensive activity of lisinopril]. 253 7

1. Although heart failure is commonly associated with depressed systolic function, there is increasing evidence that impaired diastolic performance is also universally present and might be a key determinant of symptoms, physical capacity and even survival in some subsets of patients. 2. Reduced diastolic distensibility increases cardiac filling pressure not only at rest, but even more during exercise when diastolic filling time is reduced. The increases in filling pressure and diastolic wall stress lead to pulmonary congestion and subendocardial ischaemia, it also triggers myocardial hypertrophy and a detrimental remodelling of the ventricular cavity. Perhaps even more importantly, impaired ventricular distensibility limits the use of the Frank-Starling mechanism, impairing systolic pump function and cardiac output adaptation during exercise. Therapies able to improve the distensibility of the ventricle are, therefore, desirable in heart failure. 3. Nitrates, angiotensin converting enzyme (ACE) inhibitors and diuretics may indirectly increase left ventricular chamber compliance by their effects on the right side of the heart. Cardiac glycosides do not improve myocardial relaxation and may even cause diastolic contracture at toxic doses. The new beta 1-adrenoceptor partial agonist, xamoterol, on the other hand, consistently lowers left ventricular filling pressure at rest and during exercise, and produces an increase in left ventricular dynamic compliance through the direct lusitropic effect of beta 1-adrenoceptor stimulation. These beneficial effects are maintained during prolonged therapy and also appear sufficient to slow the remodelling of the ventricular cavity. The improvement in symptoms and in exercise tolerance observed during xamoterol (Corwin, Carwin, Corwil, Xamtol, ICI 118,587) therapy might, therefore, be related to the improvement in left ventricular diastolic distensibility induced by this drug.
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PMID:Focus on diastolic dysfunction: a new approach to heart failure therapy. 257 54

1. Current therapy of heart failure leaves much to be desired. Not all patients respond, and many agents lose their effects with time. 2. Newer agents may be effective but toxic, and some which have a beneficial action when given intravenously have proved disappointing when used orally. 3. The value of digoxin in patients in sinus rhythm is open to debate, and diuretics, although useful acutely in reducing fluid overload, do not appear to improve prognosis. 4. Vasodilators increase effort capacity and reduce symptoms, possibly conferring some long-term benefit, and angiotensin converting enzyme (ACE) inhibitors improve symptoms and decrease mortality in a wide range of patients. 5. Positive inotropes may be effective in the short term, but they increase myocardial oxygen demand and show tachyphylaxis with no prognostic benefit. 6. Xamoterol (Corwin, Carwin, Corwil, Xamtol, ICI 118,587) is a partial sympathetic agonist with approximately 50% of the activity of a pure agonist, which provides inotropic support at rest, and protection against excess sympathetic activity on exercise. 7. It is compatible with other therapies and has shown no serious toxicity. 8. It should be considered at present as an adjunct to diuretic and/or ACE inhibitor therapy, although it may be useful alone; its role will become clearer as its effects on mortality are established.
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PMID:The management of heart failure and the scope for new therapies: what role for xamoterol? 257 56

The aim of the study was to investigate beta adrenoceptor modulation of norepinephrine release from sympathetic nerves in rat isolated kidney. After preincubation with [3H]norepinephrine, the renal nerves were stimulated at 1 Hz. The stimulation induced (S-I) outflow of radioactivity was taken as an index of norepinephrine release. Isoproterenol (0.1 microM) enhanced the S-I outflow of radioactivity. This effect was abolished by the beta-2 adrenoceptor blocking drug ICI 118551 (0.1 microM) but unaltered by the beta-1 adrenoceptor blocking drug atenolol (0.3 microM). In the presence of a high concentration of the angiotensin converting enzyme inhibitor captopril (5 microM), isoproterenol failed to enhance the S-I outflow of radioactivity. However, a lower concentration of captopril (0.1 microM), which totally abolished the facilitatory effect of angiotensin I (0.1 microM) on the S-I outflow of radioactivity, failed to alter the facilitatory effect of isoproterenol. Angiotensin II (0.03 microM) enhanced markedly the S-I outflow of radioactivity and in the presence of the angiotensin II receptor blocking drug saralasin (0.1 microM) this facilitatory effect was reduced markedly. Saralasin did not alter the facilitatory effect of isoproterenol. These results suggest that stimulation of prejunctional beta-2 adrenoceptors on renal sympathetic nerve endings enhances norepinephrine release. This effect is independent of local angiotensin II production and does not involve activation of prejunctional angiotensin II receptors within the rat kidney. However, the inhibitory effect of a high concentration of captopril (5.0 microM) on beta-2 adrenoceptor-mediated facilitation of norepinephrine release remains to be clarified.
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PMID:Beta adrenoceptor facilitation of norepinephrine release is not dependent on local angiotensin II formation in the rat isolated kidney. 282 55

Rats were pithed, vagotomized and adrenalectomized and the effect of procaterol on the pressor response to electrical stimulation of the thoracolumbar preganglionic sympathetic outflow from the spinal cord or to exogenous noradrenaline was studied in the absence and presence of beta-adrenoceptor antagonists and drugs interfering with the renin-angiotensin system. 1. Basal diastolic blood pressure was decreased by captopril, ramiprilate (angiotensin converting enzyme inhibitors), saralasin (an angiotensin II receptor antagonist), pepstatin A (a protease inhibitor with renin antagonistic properties) and by functional nephrectomy (ligation of both renal hili), but was not affected by procaterol (a beta 2-adrenoceptor agonist), nebivolol (a beta 1-adrenoceptor antagonist) and ICI 118,551 (erythro-dl-1-(7-methylindan-4-yloxy)-3-isopropylaminobut an-2-ol; a beta 2-adrenoceptor antagonist). 2. The vasopressor response induced by electrical stimulation of the preganglionic sympathetic nerve fibres was increased by procaterol, whereas the increase in blood pressure evoked by exogenous noradrenaline was not affected. The pressor response to both electrical stimulation and exogenous noradrenaline was decreased by captopril, ramiprilate, saralasin and nephrectomy but was not affected by nebivolol and ICI 118,551. 3. The facilitatory effect of procaterol on the neurogenic, electrically induced pressor response, which was also obtained when basal blood pressure was decreased by nephrectomy and increased by Lys8-vasopressin, was abolished by ICI 118,551 but not affected by nebivolol. Under none of these experimental conditions did procaterol alter the vasopressor response to exogenous noradrenaline. 4. The facilitatory effect of procaterol on the neurogenic, electrically induced rise in blood pressure was abolished by captopril, ramiprilate, saralasin and pepstatin A.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Probable involvement of vascular angiotensin II formation in the beta 2-adrenoceptor-mediated facilitation of the neurogenic vasopressor response in the pithed rat. 290 10

In mammalian heart tissue beta 2-adrenoceptors are known to coexist with beta 1-adrenoceptors. In the present study, evidence that beta 2-adrenoceptors in guinea-pig and rat ventricles are primarily localized on the coronary endothelium is provided by competition binding studies with the subtype-selective beta-adrenoceptor antagonists ICI 89.406 (beta 1-selective) and ICI 118.551 (beta 2-selective) on four different plasma membrane preparations. (1) Following density gradient centrifugation of cardiac ventricular microsomes from rats or guinea-pigs, endothelial plasma membranes migrated at slightly higher density than the sarcolemmal membranes, as verified by endothelial (angiotensin converting enzyme) and sarcolemmal markers (adenylate cyclase, [3H]ouabain binding). At the activity peak of angiotensin converting enzyme, the relative amount of beta 2-adrenoceptors in guinea-pigs and rats was 25% and 65%, respectively. (2) On sarcolemmal membranes corresponding to the activity peak of adenylate cyclase, beta-adrenoceptors consisted of the beta 1-type exclusively (guinea-pig), or to at least 90% (rat). (3) Cultures of coronary endothelial cells derived from guinea-pigs revealed only beta 2-adrenoceptors. (4) Isolated guinea-pig cardiomyocytes contained only beta 1-adrenoceptors, a finding recently established in rat myocytes as well.
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PMID:Cardiac ventricular beta 2-adrenoceptors in guinea-pigs and rats are localized on the coronary endothelium. 302 23

The efficacy of an early and late treatment with the angiotensin converting enzyme inhibitor lisinopril or the angiotensin II receptor blocker ICI D8731 was investigated in uninephrectomized spontaneously hypertensive rats (SHR). Rats that underwent uninephrectomy (UNX) at six weeks of age were randomly assigned to receive no treatment, lisinopril shortly after UNX, lisinopril starting 16 weeks after UNX, ICI D8731 shortly after UNX, and ICI D8731 starting 16 weeks after UNX. Blood pressure was normalized with both treatments. After six months inulin clearance was not significant different, while proteinuria and prevalence of interstitial fibrosis were significantly reduced in all treatment groups. Immunohistochemical studies revealed an interstitial, periglomerular and perivascular increase of extracellular matrix proteins in all rats, but a markedly reduced expression of collagen I, IV and fibronectin after early and late treatment compared to untreated controls. We found a significant reduction of infiltrating macrophages and T-lymphocytes in all treated animals compared to untreated controls after 2, 4 and 6 months. Especially early treatment was associated with lower numbers of infiltrating cells. Both treatments reduced proliferation of tubular and interstitial cells. There were no striking differences with regard to nephroprotection between the ACE inhibitor and angiotensin II receptor blocker. These findings show that both treatments have beneficial effects on kidney structure and function. They suggest that both ACE inhibition and angiotensin II blockade decrease renal cell proliferation and suppress the infiltration of mononuclear cells that may trigger expression of extracellular matrix proteins and progressive nephrosclerosis.
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PMID:Effects of early and late antihypertensive treatment on extracellular matrix proteins and mononuclear cells in uninephrectomized SHR. 906 7