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)

[Sar1,Phe(Br5)8] angiotensin II (Br5Ang II) is a specific, quasi-irreversible antagonist of angiotensin II (Ang II) in vitro. In vivo, this compound is a very potent, Ang II-specific antagonist with a very long duration of action against Ang II-induced blood pressure (BP) increases. In the "low-sodium" dog, this compound induces a prolonged BP reduction during and after intravenous infusion at doses comparable to cilazapril, a potent ACE inhibitor. The physicochemical and pharmacokinetic behavior of this peptide was therefore assessed to understand and interpret the prolonged antagonistic and antihypertensive activity of this peptide. Binding studies using beef adrenocortical membranes indicated specific binding of Br5Ang and related analogues to Ang II receptors with a Kd of 1.41 x 10(-9) M against iodinated [Sar1, D-Phe8]Ang II, a standard radioligand antagonist. Iodinated Br5AngII exhibited a very high degree of nonspecific binding to the membranes. It had an octanol-water partitioning coefficient of log P of + 0.903, a coefficient 84-fold higher than for [125I][Sar1, D-Phe8]Ang II. Association kinetics of [125I]Br5Ang II were similar to the standard ligand [125I] [Sar1, D-Phe8]Ang II, but the half-life of dissociation was four times higher (60 vs. 15 min at 20 degrees C). Molecular modeling indicates a practically identical conformational behavior of both peptides, Br5Ang II and [Sar1, D-Phe8]Ang II but with an expanded hydration shell over the Br5 residue. It is concluded that the prolonged duration of action is due to the increased hydrophobicity of the peptide, which leads to a slow dissociation from the Ang II receptor.(ABSTRACT TRUNCATED AT 250 WORDS)
J Cardiovasc Pharmacol 1990
PMID:An angiotensin with prolonged action and blood pressure--lowering properties. 170 28

The purpose of this study was to determine if conversion of angiotensin I to angiotensin II (Ang II) within the kidney is important in the control of renal function following sodium depletion. Infusion of a short-acting angiotensin I-converting enzyme (ACE) inhibitor, BPP5a, into the left kidney at a dose of 30 micrograms/kg/min failed to alter significantly the pressor response to Ang I administered in a femoral vein. Mean arterial pressure and renal function in the contralateral noninfused kidney also remained unchanged to intrarenal infusion of the ACE inhibitor into the left kidney. Thus, the ACE inhibitor used in these studies can be effectively localized to the renal circulation when infused intrarenally at 30 micrograms/kg/min. Intrarenal infusion of the ACE inhibitor at 30 micrograms/kg/min into sodium-restricted dogs failed to alter renal blood flow (RBF) significantly. However, the glomerular filtration rate (GFR), urine volume, and sodium excretion all increased significantly in response to intrarenal ACE inhibition. Intrarenal Ang II generation therefore appears to play a physiologically important role in the control of GFR, urine volume, and sodium excretion but not RBF following sodium depletion. The increase in GFR following intrarenal infusion of the ACE inhibitor may suggest that Ang II is formed mainly at glomerular or preglomerular sites.
J Cardiovasc Pharmacol 1990
PMID:Control of renal function by intrarenal angiotensin II in the dog. 170 31

Results of uncontrolled studies suggest that the duration of action of an ACE inhibitor may be an important determinant of renal impairment when using these agents to treat patients with heart failure. To determine whether there is experimental evidence for this hypothesis, we compared the effects of intermittent (captopril, 25 mg i.v. bolus twice daily) and continuous (captopril. 25 mg bolus, then 50 mg/day by constant infusion) ACE inhibition in an ovine model where heart failure was induced by rapid left ventricular pacing (LVP). Six sheep underwent three 4-day periods of LVP with intermittent, continuous, or no treatment (control) given in random order from the onset of LVP. Despite evidence that intermittent captopril administration allowed significant recovery of serum ACE activity (4.6 +/- 1.2 vs. 1.1 +/- 0.5 pmol/L before and after captopril bolus on day 4, p less than 0.001) and restitution of arterial pressure between successive boluses (48 +/- 7 vs. 41 +/- 4 mm Hg, p less than 0.01), there was no difference in the renal effects of intermittent and continuous ACE inhibition (creatinine clearance was 44 +/- 14 and 47 +/- 8 ml/min on day 4 of the intermittent and continuous phase, respectively). Nevertheless, there was a significant correlation between the decline in arterial pressure and fall in creatinine clearance induced by ACE inhibition (r = 0.65, p less than 0.05), with evidence that drug accumulation may potentiate hypotension and renal impairment should arterial pressure be reduced below the threshold for renal autoregulation.(ABSTRACT TRUNCATED AT 250 WORDS)
J Cardiovasc Pharmacol 1990 Oct
PMID:Renal effects of ACE inhibition in ovine heart failure: a comparison of intermittent and continuous ACE inhibition. 170 5

The clinical characteristics of the 4,170 hypertensive patients referred to the Dunedin Clinic from 1950 to 1989 have been compared for eight successive 5-year periods. A gradual decrease in the severity of referred hypertension and an increase in the proportion of patients already on treatment at the time of referral (currently 50%) were noted. For male patients, mean +/- SD initial lying blood pressure was 179 +/- 27/116 +/- 19 mm Hg in 1950-1954 and 158 +/- 25/91 +/- 14 mm Hg in 1985-1989. Corresponding prevalence data for target organ damage among male patients were retinal grade 3 or 4, 49% and 3%; cardiomegaly on chest radiograph, 60% and 26%; electrocardiogram left ventricle strain pattern, 28% and 3%; and serum urea levels greater than 10 mmol/L, 16% and 5%, respectively. For women there was a similar trend. The number of patients on drugs in each of nine categories and the percent use of each drug category for each year during 1950-1989 was recovered from computerized data files. The percentage peak usage of ganglion blockers was in 1950-1958, adrenergic neuron blockers in 1963-1970, centrally acting drugs in 1965-1968, diuretics in 1960-1982, beta-blockers in 1974-1987, alpha-blockers in 1980-1987, and angiotensin converting enzyme inhibitors and calcium antagonists in 1989. The diuretics have been the most enduring drugs, followed by the beta-blockers.
J Cardiovasc Pharmacol 1990
PMID:Changes in clinical characteristics and drug treatment of hypertension over 40 years at the Dunedin Hypertension Clinic. 170 12

Using paired isolated perfused rat tail artery segments, it was found that enalaprilat, an ACE inhibitor, augmented 1.6-fold the contractile responses to phenylephrine (PE), an alpha 1-adrenoceptor agonist. Similarly, enalaprilat potentiated 1.9-fold the alpha 1-adrenoceptor antagonist activity of doxazosin in paired rat tail artery segments. In rats treated with deoxycorticosterone acetate (DOCA) 20 mg/kg i.m. twice weekly for 5 weeks, plasma renin activity fell from a control value of 5.73 +/- 0.93 to 0.04 +/- 0.01 ng of AI/ml/h. The inhibition of circulating renin activity in these animals was associated with a loss of the potentiating effects of enalaprilat upon the alpha 1-adrenoceptor antagonist action of doxazosin. The results are interpreted as indicating that angiotensin II (AII) can modulate the functional activity of alpha 1-adrenoceptors in vascular smooth muscle.
J Cardiovasc Pharmacol 1991 Jan
PMID:Interactions between enalaprilat and doxazosin at rat tail artery alpha 1-adrenoceptors. 170 41

The effect of various antihypertensive medications on platelet function is of increasing interest. Conflicting effects of captopril on platelet function are reported and the impact of angiotensin converting enzyme (ACE) inhibitors not containing a sulfhydryl group such as enalapril, lisinopril, and quinapril on platelet function remains unstudied. Therefore, the aim of the present study was to examine the effect of antihypertensive treatment with quinapril, a novel ACE inhibitor not containing a sulfhydryl group, on platelet function. Ten white men (age range of 32-61 years) with untreated mild-to-moderate essential hypertension (supine diastolic blood pressure greater than 95 mm Hg) were treated with 4 weeks each of placebo and quinapril in a double-blind, randomized, crossover design. Quinapril (20 mg twice a day) significantly lowered systolic (p less than 0.01) and diastolic blood pressure (p less than 0.01) without any significant effect on heart rate or plasma catecholamines. No significant change was noted for in vitro platelet aggregation induced by epinephrine, ADP, or collagen. Plasma concentrations of the platelet release factors beta-thromboglobulin and platelet factor 4 did not change, nor did the platelet content of norepinephrine, platelet weight (mg/10 ml of blood), circulating platelet count, or platelet size. Thus, as assessed by a broad spectrum of platelet parameters, we found that antihypertensive treatment with quinapril has no significant effect on platelet function in patients with mild-to-moderate essential hypertension. These "platelet-neutral" properties of quinapril suggest that quinapril, both from a thromboembolic and a hemostatic point of view, may be a rather safe agent for treatment of hypertension.
J Cardiovasc Pharmacol 1991 Jan
PMID:Platelet function during antihypertensive treatment with quinapril, a novel angiotensin converting enzyme inhibitor. 170 46

Chronic hypoxia is known to be associated with a thickening of the media of pulmonary arteries. The goal of the present study was to assess if cilazapril, a novel long-acting angiotensin converting enzyme (ACE) inhibitor, could prevent this thickening. For this purpose, three groups of rats were studied. One group was kept in normal room air. Two other groups were exposed to chronic hypoxia (inspired fraction of oxygen equal to 8% during 4 weeks). One group of hypoxic rats was treated with placebo and the other group received cilazapril (as food admixture of approximately 3 mg/kg/day). After 4 weeks, rats were anesthetized and pulmonary artery pressure and hematocrit measured. Then, the lungs were perfused and fixed and morphometry of the pulmonary arteries was performed. Hypoxia induced an increase in pulmonary artery pressure and hematocrit associated with a dramatic increase in the thickness of the media of the pulmonary arteries. Cilazapril completely prevented the thickening of the media of the pulmonary arteries but did not significantly decrease the pulmonary artery pressure or right ventricular weight.
J Cardiovasc Pharmacol 1991 Jan
PMID:Effects of cilazapril, a novel angiotensin converting enzyme inhibitor, on the structure of pulmonary arteries of rats exposed to chronic hypoxia. 170 54

The aim of the present study was to look for possible additive or synergistic effects of the combined oral administration of a single dose of an angiotensin converting enzyme (ACE) inhibitor, benazepril (10 mg) (B), and a long-acting vasodilator, cadralazine (5 mg) (C), on blood pressure, arterial parameters, and active plasma renin. The study was carried out in eight normotensive subjects according to a double-blind, randomized, placebo-controlled, crossover design. Blood pressure (BP), heart rate, humeral artery diameter (D), carotid-femoral pulse-wave velocity (PWV), finger-pulse ratio (FPR), and plasma active renin (PAR) were measured at baseline and every 2 h over 8 h. A significant treatment effect was observed for supine and tilted BP, FPR, PWV, and PAR. The largest decrease in supine systolic and diastolic BP was observed with the combination (10.0 +/- 6.9/7.2 +/- 3.7 mm Hg). Six hours after drug intake, the mean changes in FPR were 0.05 +/- 0.24 (P), -0.06 +/- 0.30 (C), 0.13 +/- 0.32 (B), and 0.28 +/- 0.34 (B + C), and the mean changes in PWV were 0.14 +/- 0.66 m/s (P), 0.09 +/- 0.54 m/s (C), -0.29 +/- 0.50 m/s (B), and -0.55 +/- 0.48 m/s (B + C). PAR was more markedly augmented with the combination of the two drugs (142 +/- 40 pg/ml) than with benazepril alone (90 +/- 62 pg/ml). It was concluded that a single noneffective dose of a vasodilator administered together with an ACE inhibitor in normotensives can lower blood pressure and increase arterial compliance and plasma active renin.
J Cardiovasc Pharmacol 1991 Aug
PMID:Arterial and endocrine effects of a combination of an angiotensin converting enzyme inhibitor and a vasodilator in normotensive healthy volunteers. 171 76

We have studied the effect of ramipril (10 mg/kg daily by gastric gavage) on the development of neointima 2 and 14 days after injury to rat aorta with a balloon catheter. In treated animals, there was no significant inhibition of the early mitotic reaction after injury (synthesis of DNA, as reflected by aortic thymidine incorporation on the second day): the mean (95% confidence interval) was 3,553 (892) in the control group vs. 2,853 disintegrations/min/micrograms of DNA (555) in the treated group, 2 p greater than 0.15. However, ramipril decreased the amount of neointima formed 14 days after injury, as characterized by (a) a highly significant decrease of the intima to intima + media areas ratio [21.1 (2.4) vs. 13.7% (2.2), 2 p less than 10(-4]); (b) a significant decrease of intima-media wet weight [35.4 (1.0) vs. 30.9 mg (0.9), 2p less than 0.005]; and (c) without any significant effect on intima-media DNA content [96.3 (7.9) vs. 91.7 micrograms (5.7), 2p greater than 0.3]. These observations suggest that angiotensin converting enzyme inhibitors may not act mainly through an inhibition of smooth muscle cell proliferation. Other effects, such as inhibition of migration, hypertrophy, and matrix synthesis, should also be considered.
J Cardiovasc Pharmacol 1991 Aug
PMID:Effect of ramipril, an inhibitor of angiotensin converting enzyme, on the response of rat thoracic aorta to injury with a balloon catheter. 171 80

The purpose of this study was to determine efficacy and safety of the angiotensin converting enzyme inhibitor, cilazapril, in the treatment of hypertensive diabetics with renal insufficiency. Fifteen type II diabetics with hypertension and chronic renal insufficiency aged (mean +/- SD) 64 +/- 7 years were studied in a regional clinic and university hospital hypertension unit. The blood pressure was measured biweekly. Urinary collections were done after 2 weeks of placebo and 8 weeks of cilazapril treatment. The blood pressure decreased from 176 +/- 15/105 +/- 9 to 164 +/- 11/95 +/- 9 mm Hg and serum creatinine from 197 +/- 69 to 179 +/- 73 mumol/L. The creatinine clearance rose from 41.6 +/- 11.4 to 47.4 +/- 14.9 ml/min, while protein excretion decreased from 0.8 +/- 1.3 to 0.5 +/- 0.8 g/24 h (p less than 0.05). The blood pressure change was inversely correlated with the creatinine clearance change (r = -0.5, n = 15, p less than 0.05). In these high-risk patients, 8 weeks of cilazapril treatment improved both blood pressure control and renal function but renal function improved most in the patients whose blood pressure changed the least.
J Cardiovasc Pharmacol 1991 Sep
PMID:Improved kidney function with cilazapril in hypertensive type II diabetics with chronic renal failure. 172 Aug 32


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