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)

We assessed vascular and hormonal responses to inhibition of peptidyldipeptide hydrolase, which converts angiotensin I to angiotensin II (converting enzyme) and degrades bradykinin (kininase II), in subjects given 10 meq of sodium to activate both systems. In nine normal subjects a threshold dose of 30 MICROgram per kilogram of the inhibitor, SQ 20881, modestly influenced mean blood pressure (-5 +/- 1 mm Hg, P less than 0.05), and renal blood flow (+50+/-8 ml per 100 g per minute), plasma renin activity (+ 2.3 +/- 0.6 ng per milliliter per hour), and angiotensin II (-11 +/- 3 pg per milliliter) more strikingly (P less than 0.01). In six patients with essential hypertension the threshold inhibitor dose was reduced to 10 microgram per kilogram; 30 kilogram per kilogram had an enhanced (P less than 0.01) effect on mean blood pressure (-11 +/- 2 mm Hg), renal blood flow (137 +/- 20 ml per 100 g per minute), and angiotensin II concentration (-29 +/- 12 pg per milliliter). SQ 20881 elevated plasma bradykinin concentration (7.4 +/- 2.6 ng per milliliter, P less than 0.02) only in the hypertensive patients. Because both renin-angiotensin and kallikrein-bradykinin systems are influenced, vascular responses to SQ 20881 must be interpreted cautiously, but this agent has excellent antihypertensive characteristics.
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PMID:Accentuated vascular and endocrine response to SQ 20881 in hypertension. 19 3

1. Captopril was shown to be as effective as hydrochlorothiazide in lowering the blood pressure in patients with moderately severe essential hypertension. 2. With the combination of captopril and hydrochlorothiazide satisfactory control of blood pressure was maintained over 8 months. 3. Inhibition of angiotensin converting enzyme by captopril in man was associated with falls in plasma angiotensin II and urinary aldosterone and rises in angiotensin I and plasma renin. 4. No change in venous concentrations of bradykinin could be demonstrated during therapy. 5. Captopril attenuated the hyperaldosteronism and hypokalaemia associated with diuretic therapy.
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PMID:Hormonal changes with long-term converting-enzyme inhibition by captopril in essential hypertension. 23 17

Patients with essential arterial hypertension demonstrate abnormal vasodilator capacity either during increased cardiac metabolic demand or during pharmacological vasodilation. Structural and functional damage to the coronary microcirculation has been proposed as one of the major causes of impaired coronary reserve in this disease. To assess the role of microvascular impairment in regional myocardial blood flow (MBF), 27 patients with essential hypertension were evaluated by dynamic positron emission tomography (PET) at rest, during atrial pacing and after dipyridamole infusion and compared with 13 healthy subjects. All patients had normal coronary arteries, 17 had moderate to severe hypertension and 10 had mild hypertension. Baseline mean MBF of 0.97 +/- 0.25 ml/min/g was significantly increased to 1.60 +/- 0.38 during atrial pacing and 2.35 +/- 0.95 after dipyridamole infusion (p < 0.01); however, mean flow during atrial pacing and after dipyridamole infusion was significantly lower than in healthy subjects (2.15 +/- 0.73 and 3.71 +/- 0.86 ml/min/g, p < 0.05 and p < 0.01, respectively). The MBF response to atrial pacing and dipyridamole infusion was similarly depressed in patients with mild and severe hypertension. The study was repeated after 6 months of antihypertensive treatment with the calcium antagonist verapamil or the angiotensin converting enzyme (ACE) inhibitor enalapril in a subgroup of 20 patients as part of a randomised, single-blind clinical trial. This study is still in progress; the initial 16 patients treated with verapamil or enalapril showed an obvious improvement in MBF values during atrial pacing and after dipyridamole infusion after 6 months of therapy (mean MBF: 2.10 +/- 0.64 and 2.99 +/- 1.63 ml/min/g, respectively, p < 0.05 vs pretreatment values). In conclusion, obvious impairment of MBF during atrial pacing and after dipyridamole infusion was observed in hypertensive patients with normal coronary arteries and this appeared unrelated to the severity of hypertension. Therapy with verapamil or enalapril improved coronary reserve and MBF response to an increase in myocardial oxygen demand.
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PMID:Regional myocardial blood flow and coronary reserve in hypertensive patients. The effect of therapy. 128 84

Diabetes mellitus (DM)-linked metabolic alterations and hypertension concomitantly accelerate or precipitate cerebrovascular and coronary heart disease, nephropathy, retinopathy and widespread macroangiopathy, thereby conferring to diabetic patients a very high risk of morbidity, disability and early death. Therefore, the long-term care for diabetic patients should be aimed at concomitant metabolic and blood pressure (BP) control. Dietary measures are indispensable; a high fibre, low fat, low salt diet is recommended, complemented with caloric restriction and physical exercise when body weight is above the ideal. Antidiabetic pharmacotherapy involves an unresolved dilemma. The desired achievement of euglycemia necessitates effective levels of insulin, but hyperinsulinemia (due to parenteral [over]treatment in insulin-dependent DM) is suspected to promote atherogenesis and represents a coronary risk factor and perhaps even facilitates hypertension. Considering antihypertensive pharmacotherapy, thiazide-type or loop diuretics are problematic drugs in DM because they can aggravate metabolic alterations. These agents also seem to exert only a limited preventive or regressive effect on left ventricular hypertrophy (LVH); beta-blockers are also not considered ideal, since they decrease the awareness of hypoglycemia and tend to promote glucose intolerance. Unselective beta-blockers in particular promote peripheral ischemia and insulin-induced hypoglycemia, while beta-blockers without intrinsic sympathomimetic activity lower serum HDL-cholesterol. Calcium antagonists and ACE inhibitors have equivalent antihypertensive efficacy, do not impair carbohydrate and lipid homeostasis or peripheral perfusion and can effectively improve LVH. Certain ACE inhibitors may even slightly ameliorate abnormal insulin sensitivity and plasma glucose levels. While alpha-blockers share most of these desirable properties, these agents are more prone to precipitate orthostatic hypotension in the diabetic patient. The non-thiazide diuretic indapamide and the serotonin2-antagonist ketanserin also combine antihypertensive efficacy with metabolic neutrality. The ultimate goal of therapy is to improve life prognosis. In essential hypertension, conventional drug treatment based on diuretics in high dosage satisfactorily reduced cerebrovascular but not coronary complications or sudden death. In diabetic patients, the influence of antihypertensive therapy on prognosis has not been assessed prospectively. Based on retrospective analyses, Warram et al reported a 3.8 times higher mortality in diabetics treated with diuretics alone, than in diabetics with untreated hypertension (Arch Intern Med. 1991;151:1350). H. H. Parving calculated that effective BP control in patients with diabetic nephropathy might reduce 10 year-mortality from about 65 to 20 percent (J Hypertension. 1990; 8[Suppl 7]:187).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Antihypertensive therapy in diabetic patients. 128 10

Glucose intolerance and noninsulin-dependent diabetes are commonly associated with hypertension. Epidemiological data suggest that this association is independent of age and obesity. Much evidence indicates that the link between diabetes and essential hypertension is hyperinsulinemia. When hypertensive patients whether obese or of normal weight are compared with matched normotensive control subjects, an increased plasma insulin response to a glucose challenge is consistently observed. Studies using insulin glucose clamp techniques in combination with tracer glucose infusion and indirect calorimetry have demonstrated that the insulin resistance in hypertensive subjects is located in muscles and restricted to glycogen synthesis. The relations between hyperinsulinemia and blood pressure do not prove that the relationship is a causal one. However, at least four mechanisms may link hyperinsulinemia with hypertension: Na+ retention, sympathetic nervous system overactivity, disturbed membrane ion transport and proliferation of vascular smooth muscle cells. Diuretics and beta-blockers may enhance insulin resistance, which is not affected by calcium antagonists, but decreased by the ACE inhibitor captopril. Weight reduction and regular physical exercise can improve insulin sensitivity and decrease blood pressure values. These nonpharmacological interventions should be more strongly recommended to diabetic and nondiabetic hypertensive patients.
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PMID:Hyperinsulinemia, insulin resistance and essential hypertension. 130 12

To determine the haemodynamic profile of angiotensin converting enzyme (ACE) inhibitors during stress, the cardiovascular response to various stress tests was examined in patients with essential hypertension before and after three months of therapy with lisinopril. Eighteen white patients were enrolled in the trial, of whom 12 completed the protocol. ACE inhibition with lisinopril effectively reduced systolic and diastolic pressure in the office (P less than 0.001), at rest (P less than 0.002), during mental stress (P less than 0.003), cold pressor test (P less than 0.003), and reaction time task (P less than 0.05). During physical exercise only diastolic pressure was significantly reduced (P less than 0.02). The fall in peak systolic pressure during cold pressor test and reaction time task was more pronounced than the fall in casual systolic pressure (P less than 0.05). At rest, cardiac output was unchanged, but total peripheral resistance was reduced after medication with lisinopril (P less than 0.05). During the cold pressor test, the increase in total peripheral resistance was attenuated by ACE inhibition (P less than 0.04). The haemodynamic response profile was not altered during the other tests. It is concluded that in middle-aged men ACE inhibitors reduce blood pressure during a variety of stressful events without altering the haemodynamic profile and even attenuating vasoconstriction during stress. This response pattern to ACE inhibition with lisinopril may reduce the impact of recurring stress-induced increases of blood pressure and of exaggerated vasoconstrictive stimuli on the cardiovascular system.
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PMID:Impact of angiotensin converting enzyme inhibition on the haemodynamic profile during laboratory stress tests. 132 Dec 47

Angiotensin converting enzyme inhibitors are utilized in the treatment of essential hypertension and of chronic cardiac failure. They are also employed in the treatment of the myocardial lesion of ischemia-reperfusion, which involves oxygen free radicals. In the present study we investigated the possibility of three angiotensin converting enzyme inhibitors (captopril, enalapril, lisinopril) to act as hydroxyl radical scavengers. The rate constants for reactions of those compounds with .OH were determined using the deoxyribose method. All there compounds proved to be good scavengers of .OH with rate constants of about 10(10)M-1s-1 and are iron chelators specially enalapril. The fact that captopril possesses a thiol group does not confer an higher antioxidative capacity. These results suggest that scavenging of oxygen free radicals may be a possible mechanism contributing to the therapeutic effect of angiotensin converting enzyme inhibitors.
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PMID:[Angiotensin-converting enzyme inhibitors as neutralizers of hydroxyl radical]. 132 14

The presence of slightly increased urinary albumin excretion (UAE), even at levels well below levels detectable by an ordinary dipstick, has been suggested as a predictor of cardiovascular morbidity and as a reflection of the degree of overall vascular permeability. The aim of the present investigation was to study the effects of two different antihypertensive drug regimens, an ACE inhibitor and a beta-adrenoceptor antagonist, on the low UAE rate observed in subjects with uncomplicated, mild to moderate primary hypertension. After a 4-week placebo run-in period, 49 patients (mean age 54 y) were randomly assigned in a double blind manner either to further 4 weeks on placebo (P, n = 15), 8 weeks on lisinopril (L, n = 17; 20 mg/40 mg o.d.) or 8 weeks on atenolol (A, n = 17; 50 mg/100 mg o.d.). The 24-h UAE was measured every second week. At entry and after 4 weeks the glomerular filtration rate and the renal plasma flow were measured. Both drugs lowered blood pressure (BP) to a similar extent after 4 and 8 weeks of treatment; the blood pressures were 160/106 (P), 159/104 (L) and 154/103 (A) at entry, and 133/83 (L) and 134/87 (A) at the end of the study after 8 weeks. On entry the 24-h UAE in all patients ranged from 4 to 49 mg (mean 14.1 mg), and it did not differ significantly between groups.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A comparative study of lisinopril and atenolol on low degree urinary albumin excretion, renal function and haemodynamics in uncomplicated, primary hypertension. 133 63

These studies were undertaken to evaluate different manifestations of structural cardiovascular changes and the effects of antihypertensive therapy in essential hypertension. A meta-analysis of 109 studies that had examined the effect of different pharmacological blood pressure lowering regimens on left ventricular structure, examined by echocardiography, was undertaken to increase the statistical power, to resolve uncertainty and to improve the accuracy of estimation of the magnitude of effect. Strict preset criteria were applied. The effect of different drugs in monotherapy and in particular first line antihypertensive therapies were compared, using an analysis of covariance (ANCOVA). ACE-inhibitors, beta-blockers and calcium antagonists all reduced left ventricular mass (LVM) through a reduction in wall hypertrophy, the effect being most pronounced with ACE-inhibitors. Conversely, diuretics reduced LVM mainly through a reduction of left ventricular volume. Previously untreated males (n = 28, 86 kg, 46 years, 27 kg/m2) with non-malignant essential hypertension (supine diastolic blood pressure (DBP) > 95 mmHg 3-4 times (in triplicate) on placebo) were randomized to long-term double-blind treatment with enalapril (E) or hydrochlorothiazide (H). There were no significant differences between the groups at baseline. Vascular alterations in the retina (eyeground photo, refined grading), cardiac morphology (M-mode echocardiography, ASE), structural vascular changes of the hand (plethysmography, minimal resistance (Rmin)), total peripheral resistance ((TPR), calculated from dye-dilution) and blood pressure (intraarterial) were significantly interrelated at baseline except LVM and Rmin. After 6 months of therapy, E reduced the signs of vascular changes in the retina as well as Rmin in the hand circulation, while H did not change or increased these structural vascular changes. The blood pressure lowering effect of E (mainly through lowering of TPR) tended to be more pronounced, measured both intraarterially and indirectly, than that seen with H (mainly through lowering of cardiac output), however, there were no significant differences. LVM decreased progressively with E while the effect of H was non-significant. E reduced wall thickness but not left ventricular diameter and also improved left ventricular distensibility significantly. The effect on cardiac morphology was significantly different between therapies when taking change in blood pressure into account. After the longest follow-up on monotherapy (18 months) E had reduced LVM by 2.7 g/mmHg and H (14 months) by 1.3 g/mmHg (significant for E only). In univariate analysis the changes in cardiovascular structure were significantly related to the changes in the Renin-Angiotensin-Aldosterone System (RAAS).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Structural cardiovascular changes in essential hypertension. Studies on the effect of antihypertensive therapy. 134 61

In view of the likely prohypertensive effects of hyperinsulinemia and the presence of insulin resistance in primary hypertension, the effects of various antihypertensive therapies on insulin sensitivity need to be identified. The evidence strongly supports major beneficial effects of weight reduction and aerobic exercise. Deleterious effects have been shown for diuretics and most beta-blockers, whereas probable beneficial effects have been seen with alpha-blockers, one angiotensin converting enzyme inhibitor, and various calcium entry blockers. Improvement of insulin sensitivity and reduction of plasma insulin levels are desirable attributes of antihypertensive therapy that should be more carefully considered in the future.
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PMID:Effects of antihypertensive therapy on insulin resistance. 134 22


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