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 risk for cardiovascular complications is already substantially increased in persons with borderline elevation of arterial pressure (141-159/90-94 mmHg and transiently below). It increases progressively with higher grades of hypertension. The main aim of treatment is thus a significant improvement in survival for the patient. Persons with raised blood pressure (BP) have often additional cardiovascular risk factors such as deranged carbohydrate metabolism, dyslipidemia, left ventricular hypertrophy, smoking and others. Treatment of hypertensive patients should thus not only normalize BP but should at the same time reduce associated risk factors or at least not increase them. Conventional antihypertensive treatment based on thiazides in high doses or beta-blocking agents led to marked reduction of strokes and heart failure, but did not satisfactorily reduce coronary heart disease or sudden cardiac death. It has been suspected that other cardiac risk factors are insufficiently influenced or eventually even deteriorated by conventional therapy, thus counteracting partly a beneficial effect of lowered BP. Beta-blockers however have at least a secondary preventive effect after myocardial infarction. Newer antihypertensive drugs such as ACE-inhibitors, calcium antagonists and alpha 1-blockers reduce left ventricular hypertrophy and are at least neutral with regard to metabolism of lipids and carbohydrates. The non-thiazide diuretic indapamide and the serotonin (S2-) blocker ketanserin likewise are neutral with regard to glucose and lipid metabolism. The efficacy of these new drugs regarding long term survival is as yet undetermined. Persisting borderline or established hypertension should as a rule always be approached with basic non-pharmacologic measures: loss of overweight, reduction of alcohol intake, exercise, avoidance of high salt foods, abstention from smoking and withdrawal of BP-raising drugs. If antihypertensive medication is indicated, potential first line drugs are ACE-inhibitors, calcium antagonists, beta-blockers, thiazides at low dose, indapamide, ketanserin, the alpha 1-blocker prazosin and others; initially as monotherapy, if needed in combinations of 2 or 3. Older patients or those will with additional disturbances such as diabetes, hypercholesterolemia, nephropathy, heart failure, ischemic heart disease, arrhythmias, claudication, asthma and others need problem-adjusted modifications of treatment.
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PMID:[Antihypertensive therapy in the nineties]. 153 54

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

1. We studied the renal effects of reinfusing low dose angiotensin II (1 ng kg-1 min-1) into seven salt-replete healthy volunteers after pretreatment with the angiotensin converting enzyme (ACE) inhibitor captopril (25 mg) to establish whether the natriuretic and renal haemodynamic responses to ACE inhibition in normal man result from suppression of circulating angiotensin II. In the same subjects we also studied the effect of captopril (25 mg) with and without exogenous angiotensin II (1 ng kg-1 min-1) on the natriuretic response to intravenous frusemide (20 mg). 2. In the pre-frusemide study captopril increased absolute and fractional excretion of sodium and paraaminohippurate clearance but had no effect on inulin clearance. 3. Reinfusion of angiotensin II after captopril pretreatment completely suppressed the renal effects of ACE inhibition, yielding renal vasoconstrictor and antinatriuretic effects equivalent to those produced by infused angiotensin II in the absence of captopril. 4. Frusemide increased renal sodium excretion without affecting paraaminohippurate or inulin clearance. Captopril augmented frusemide-induced natriuresis and again this effect was reversed by angiotensin II reinfusion. 5. We conclude that captopril augments both basal and frusemide-induced renal sodium excretion in normal man. Our findings suggest that these renal responses to ACE inhibition may be mediated by inhibition of circulating angiotensin II, specifically its renal tubular salt-retaining actions, rather than via effects on other neurohumoral systems.
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PMID:Captopril augments both basal and frusemide-induced natriuresis in normal man by suppression of circulating angiotensin II. 163 64

Previous studies have shown that hamsters have low spontaneous intakes of NaCl solutions and are refractory to induction of salt appetite. In order to examine the generality of these results, the intakes of NaCl and NaHCO3 solutions are reported for hamsters housed either in normal laboratory conditions (sedentary) or with free access to exercise wheels. Spontaneous salt intakes, as well as those induced by acute sodium depletion and treatment with either the angiotensin converting enzyme inhibitor, enalapril, or deoxycorticosterone acetate (DOCA), were measured. The intakes of NaCl and NaHCO3 were similar. Salt intakes tended to be lower in exercising than in sedentary groups. Neither acute sodium depletion nor administration of enalapril increased salt intake systematically, but treatment with DOCA increased intakes of both salt and water. These results are contrasted with the efficacy of all three treatments to induce salt appetite in rats.
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PMID:Effects of exercise and anion on intake of sodium solutions in Syrian hamsters. 165 67

We investigated the linkage between high blood pressure and the ACE gene in the F2 generation between SHRSP/Izm and WKY/Izm. The male F2 rats were categorized into 3 genotypes according to a microsatellite polymorphism in the ACE gene. Significantly high blood pressure was observed in the SHRSP homozygotes when it was compared to the blood pressure of the heterozygotes. Further, after 2 or 3 months salt-loading, the blood pressure was significantly higher in the SHRSP homozygotes than in the heterozygotes and the WKY homozygotes. The heterozygotes had a blood pressure similar to that in the WKY homozygotes, indicating that the effect of the ACE gene genotype was recessive. Salt appetite was neither correlated with the salt-sensitivity nor cosegregated with the ACE genotype. The results indicate that the locus of ACE gene associates with the development of hypertension, especially salt-sensitive hypertension.
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PMID:Blood pressure cosegregates with a microsatellite of angiotensin I converting enzyme (ACE) in F2 generation from a cross between original normotensive Wistar-Kyoto rat (WKY) and stroke-prone spontaneously hypertensive rat (SHRSP). 166 4

There is controversy as to which BP-lowering manoeuvres and/or drugs can be combined effectively. Ideally, a combination therapy should show an additional BP-lowering effect over monotherapy. The effect should be of sufficient clinical significance, without short- or long-term adverse effects, and the patients should feel well. Combination therapy should be based on the understanding of the mechanisms of action of the different classes of drugs used and of their interaction. Rational combinations include an ACE inhibitor or a beta-blocker together with moderate salt restriction or a thiazide diuretic or a calcium antagonist. Less rational combinations include an ACE inhibitor with a beta-blocker, and a calcium antagonist with a thiazide diuretic.
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PMID:Combination therapy in hypertension. 168 67

In our studies, we investigated the vasodepressor effects of bradykinin in vivo in normotensive and hypertensive subjects. Bradykinin was injected intravenously and intra-arterially (40-6,050 pM/kg) and was infused intra-arterially (40-6,050 pM/kg/min). The investigations were performed in 21 normotensive and 15 hypertensive patients. Bradykinin injections were performed after the following pharmacological interventions: salt restriction (10 mmol of Na/day), salt loading (300 mmol of Na/day), captopril (50 mg), ramipril (5 mg), lisinopril (20 mg), ketotifen (2 X 1 mg), indomethacin (2 X 50 mg), and propranolol (80 mg). The results show that bradykinin lowers blood pressure in a dose-related manner by marked reduction in peripheral vascular resistance. The blood pressure reduction was strongly correlated with the increase in kinin concentration. This effect of bradykinin appears to be independent of changes in sodium metabolism, beta-adrenoceptors, histamine-1 receptors, and prostaglandins. ACE inhibitors protentiate the blood pressure-lowering effect of bradykinin approximately 20- to 50-fold. In the case of intra-arterial injection of bradykinin, only 2-5% of the intravenously used dose of bradykinin are needed to produce an identical fall in blood pressure. From these experiments, a pulmonary clearance rate of bradykinin of over 95% can be calculated. In the pulmonary arteries, bradykinin has no effect on vascular resistance. In patients suffering from primary or renovascular hypertension, the blood pressure response to bradykinin was enhanced. The bradykinin potentiating effect of the ACE inhibitors was not altered in the hypertensives. In patients suffering from borderline hypertension or primary hyperaldosteronism, bradykinin caused the same blood pressure lowering effect as in the normotensives.
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PMID:Hemodynamic effects of bradykinin on systemic and pulmonary circulation in healthy and hypertensive humans. 169 61

Angiotensin II has previously been reported to have in vivo and in vitro cardiac hypertrophic effects. We used the salt-sensitive Dahl rat genetic strain to separate mechanical (pressure overload) vs. hormonal (renin-angiotensin system) input in cardiac hypertrophy. Blood pressure was significantly increased and left ventricular hypertrophy, as indexed by LV/BW ratios, was present at 7 and 15 days in rats receiving 4% and 8% NaCl compared to the 1% controls. There was no effect of the angiotensin converting enzyme inhibitor, enalapril maleate, on lowering the blood pressure in 8% NaCl-treated animals, however, there was a significant reduction in LV/BW ratio in 8% NaCl-treated animals that received this drug. Left ventricular angiotensinogen mRNA activity was significantly reduced in rats receiving 4% and 8% NaCl. In this model of hypertension the cardiac hypertrophy which develops is largely dependent on mechanical forces though there remains a significant contribution to this process from either circulating or localized angiotensin II production. Regulation of angiotensinogen gene expression in the hypertrophied left ventricle suggests that volume and electrolyte control of angiotensinogen gene expression in the heart and/or hereditary factors are predominant in the control of regulation of this gene in the left ventricle of Dahl rats.
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PMID:Angiotensin converting enzyme inhibition in Dahl salt-sensitive rats. 171 20

Arterial hypertension is frequently associated with metabolic abnormalities. Hyperinsulinemia and insulin resistance are found in obese patients, in non-insulin-dependent diabetics and in some hypertensive patients, irrespective of whether the patients are overweight or have diabetes mellitus. Membrane transport abnormalities, such as increased sodium-lithium exchange associated with hypertension are also significantly related to disturbances in lipid metabolism. Increased sympathetic nervous system activity is a well established feature of arterial hypertension and this may also affect glucose and lipid metabolism. The possibility of these metabolic alterations in the hypertensive patient must be taken into account when deciding upon treatment. Attention to diet is mandatory and includes advice to reduce energy, salt and saturated fat intakes and to increase the intake of less digestible fiber and of potassium; alcohol consumption should be limited. Energy expenditure by regular aerobic physical exercise should be encouraged and continuous effort is necessary to help patients stop smoking. In patients with high blood pressure and abnormalities in lipid and glucose metabolism, it is wise to start pharmacological treatment with drugs that are known to be neutral in their metabolic effects, such as calcium antagonists, angiotensin converting enzyme inhibitors or alpha-blocking agents.
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PMID:Metabolic disturbances and antihypertensive therapy. 179

Effect of angiotensin converting enzyme inhibitor (ACEI) and calcium channel blockers (CaB) on renal blood flow (RBF), glomerular filtration rate (GFR), and autoregulation (AR) of RBF were studied on the uninephrectomized spontaneously hypertensive rat (SHR) under the conditions of high (H) and low (L) salt loading. SHR was given with 0.9% or 0.09% NaCl solution as drinking water (GH, GL). Each group was divided into three groups for treatment with enalapril (Enp) and nitredipine (Nit); i.e. Enp group (GHE, GLE), Nit group (GHN, GLN) and control group (GHC, GLC). After 6 weeks, inulin clearance (Cin) was determined and RBF was measured by means of an electromagnetic flow meter. The renal arterial pressure was lowered by clamping and changes in RBF and AR were examined. Cin showed higher values of 1.85 and 1.69 ml/min in GHN and GLN, as compared to be 1.33 and 1.28 ml/min in GHC and GLC (p less than 0.01). Filtration fraction (FF) showed lower values of 0.18 and 0.20 ml/min in GHE and GLE (p less than 0.01), whereas 0.29 and 0.30 in GHC and GLC respectively. RBF was markedly lower at 7.4 ml/min in GLC as compared to 9.9 ml/min in GHC (p less than 0.01). In GH, GHE showed a higher value of 11.6 ml/min, as compared to GHC (p less than 0.01). In GL, comparing with GLC the value was much higher of 12.1 ml/min in GLE (p less than 0.01). AR of RBF diminished in GLC at higher blood pressure as compared to GHC (p less than 0.01). It was maintained at lower blood pressure in GLE (p less than 0.01), but there were no significant differences between four groups; i.e. GLN, GHC, GHE and GHN. In summary, low salt loading reduced RBF and suppressed AR. Enp elevated RBF, lowered FF and caused AR to be maintained even at lower blood pressure. Nit elevated RBF and GFR without changing FF, and did not suppress AR. These results indicate that, in hypertension complicated with moderate dysfunction, both ACEI and CAB are expected to exhibit the beneficial effects on maintenance of renal circulation, despite though the different mechanism.
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PMID:[Effect of angiotensin converting enzyme inhibitor and calcium channel blocker on renal function of spontaneously hypertensive rat]. 180 67


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