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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In ten patients with angiographically demonstrated coronary heart disease exercise electrocardiograms were recorded before as well as two and four hours after administration of 5 or 10 mg Quinapril, an angiotensin converting enzyme inhibitor (ACEI). This reduced the sum of ST-segment depressions from 16.3 to 11.6 mV (P less than 0.001). While the heart rate remained unchanged, blood pressure fell from 147/91 to 119/79 mm Hg and the angina-free exercise time was clearly prolonged. Altogether there was a reduction of the ischaemia reaction by 35%. This perhaps speaks for an anti-anginal effect of ACEI, which could be of importance in the management of both hypertension and heart failure. In addition, the ACE inhibitors might be used as anti-angina drugs.
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PMID:[Angiotensin-converting enzyme inhibitors in angina pectoris]. 335 81

Following systemic absorption, quinapril is converted by de-esterification to quinaprilat (the active diacid metabolite), an inhibitor of angiotensin converting enzyme (ACE). Pharmacodynamic studies in animals indicate inhibition of ACE both in plasma and at tissue sites, such as the arterial wall and heart, following administration of quinapril. Tissue ACE inhibition may be an important component of the mechanism of action of quinapril (and other ACE inhibitors) in achieving favourable effects in cardiovascular disorders. Quinaprilat has a short elimination half-life (approximately 2 hours), but binds potently to and dissociates slowly from ACE, thus allowing once or twice daily administration of quinapril in the treatment of patients with hypertension or congestive heart failure. Quinapril 10 to 40 mg/day has achieved adequate control of blood pressure in most patients with essential hypertension in clinical trials. Some patients required quinapril dosages up to 80 mg/day and/or concomitant diuretic therapy. Titrating quinapril dosages from 10 to 40 mg/day increased response rates without increasing the incidence or severity of adverse events. Addition of hydrochlorothiazide to quinapril therapy improved response rates by approximately 10 to 20% in patients with hypertension. In general, blood pressure control with quinapril monotherapy was similar to that achieved with enalapril or other standard antihypertensive agents in comparative trials. Quinapril < or = 40 mg/day improved exercise tolerance, reduced the severity and frequency of symptoms, and improved functional (New York Heart Association) class in most clinical studies of patients with congestive heart failure. In addition, beneficial haemodynamic and echocardiographic changes achieved with quinapril were maintained for up to 1 year with continued administration to such patients, but its effect on survival in patients with congestive heart failure has not been reported. The tolerability profile of quinapril is broadly similar to that of other ACE inhibitors; pooled data from clinical trials indicated that 12% of patients with hypertension or congestive heart failure receiving quinapril experienced a treatment-related adverse effects compared with 15% of enalapril recipients and 16% of captopril recipients. Thus, quinapril has clearly established a role as an effective and well tolerated alternative to other ACE inhibitors for the treatment of hypertension and congestive heart failure. While effects of quinapril on survival of patients with congestive heart failure have not been determined, large intervention studies have demonstrated improved mortality rates with other ACE inhibitors. Further studies, including a large ongoing trial of normotensive patients with coronary artery disease but normal left ventricular function, may also establish a role for quinapril in treating patients with ischaemic heart disease.
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PMID:Quinapril. A reappraisal of its pharmacology and therapeutic efficacy in cardiovascular disorders. 752 26

To investigate the metabolic and renal effects of the nonsulfhydryl, tissue-active ACE inhibitor quinapril in diabetes and in hypertension, we studied 30 essential hypertensives and 24 non-insulin-dependent (type II) diabetic (NIDDM) subjects with hypertension. Systolic and diastolic blood pressures, plasma glucose, and insulin responses to an oral glucose load (75 g), lipid profile, and urinary albumin excretion were evaluated before and after 8 weeks' administration of quinapril (10 to 40 mg/day). Quinapril produced a significant and comparable reduction of arterial blood pressure in both groups. Mean arterial pressure decreased from 114.8 +/- 0.9 to 94.2 +/- 1.1 (-17.9 +/- 1.5%) in the essential hypertensive group and from 118.4 +/- 1.6 to 96.2 +/- 1.4 (-18.4 +/- 1.6%) in the diabetic hypertensive group. In both essential hypertensives and diabetic-hypertensive subjects with microalbuminuria, quinapril significantly and comparably reduced the urinary albumin excretion rate (UAE); UAE decreased from 32.5 +/- 5.5 micrograms/min to 14.7 +/- 3.7 micrograms/min (P < .05 v baseline) in the diabetic-hypertensive group and from 27.5 +/- 3.0 micrograms/min to 11.6 +/- 2.7 micrograms/min (P < .05 v baseline) in the essential hypertensives. Altogether, a direct correlation was found between the initial level of UAE and the UAE reduction after quinapril (delta UAE) (r = 0.706, p < .05). Insulin and glucose responses to an oral glucose tolerance test and the lipid profiles were not modified by quinapril treatment. The results confirm that quinapril is an effective antihypertensive agent that additionally reduces microalbuminuria in both hypertensive diabetics and in patients with essential hypertension, without altering insulin sensitivity and lipid profiles.
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PMID:Quinapril reduces microalbuminuria in essential hypertensive and in diabetic hypertensive subjects. 757 97

Loss of renal functional reserve, that is, absence of the glomerular vasodilatory response to amino-acid infusion, has been interpreted as equivalent to glomerular hyperperfusion/hypertension, and therefore proposed as a marker of high risk for progressive glomerular sclerosis. To substantiate the validity of this hypothesis we evaluated the renal response to glycine and the extent of glomerular damage 10-12 weeks after induction of anti-glomerular basement membrane glomerulonephritis with or without superimposed clip hypertension. Untreated rats and rats chronically treated with quinapril, a converting-enzyme inhibitor, were studied. In untreated groups, loss of renal functional reserve was demonstrated since GFR, single-nephron GFR (SNGFR) and plasma flow (SNPF) did not increase during glycine infusion. The absence of renal reserve was associated with glomerular hyperfusion/hypertension, and development of proteinuria and glomerulosclerosis. Quinapril reduced proteinuria and diffuse sclerosis in anti-glomerular basement membrane GN, and decreased blood pressure and segmental glomerulosclerosis in antiglomerular basement membrane GN with superimposed clip hypertension. Both treated groups demonstrated a restoration of renal functional reserve, as depicted by increases in GFR, SNGFR, and SNPF after glycine, despite persistence of glomerular hyperperfusion/hypertension. These data demonstrate that renal functional reserve testing, although it does not detect glomerular hyperperfusion/hypertension, can provide information on the progression of glomerular damage.
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PMID:Renal functional reserve in experimental chronic glomerulonephritis. 781 49

The antihypertensive activity of quinapril was examined in normotensive and various hypertensive animal models. In 2-kidney, 1-clip renal hypertensive rats (2K-RHR), quinapril (0.1 to 1.0 mg/kg, p.o.) had a dose-related and sustained antihypertensive action, which was as potent as that of enalapril and approximately 40 times stronger than that of captopril. Heart rate was not changed by these doses of quinapril. In spontaneously hypertensive rats (SHR) and 1-kidney, 1-clip renal hypertensive rats, quinapril as well as enalapril dose-dependently produced a significant fall in blood pressure. The relative potency and duration of the effect of quinapril was the same as that of enalapril in these models. Quinapril at 30 mg/kg, p.o. lowered blood pressure and increased heart rate in normotensive rats. In contrast, quinapril and enalapril failed to reduce blood pressure in DOCA/salt hypertensive rats. In the repeated dose study, no development of tolerance was observed during the administration period in 2K RHR and SHR. The antihypertensive effects in 2K RHR was greater than those in SHR. Quinapril was more potent and long-lasting than enalapril in 2K RHR and SHR. From these results, quinapril is expected to be useful for the clinical treatment of hypertension.
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PMID:[Antihypertensive activity of the angiotensin converting enzyme inhibitor quinapril HCl: (S)-2-[(S)-N-[(S)-1-ethoxycarbonyl-3-phenylpropyl) alanyl]-1,2,3,4- tetrahydro-3-isoquinolinecarboxylic acid monohydrochloride in various hypertensive animal models]. 833 86

1. Forty patients with moderate to severe hypertension and daytime ambulatory diastolic blood pressure > or = 90 mm Hg were randomized double-blind to once-daily treatment with either quinapril up to 20 mg (n = 20) or atenolol up to 100 mg (n = 20) as single drugs or in combination with hydrochlorothiazide 25 mg over a period of 12 weeks. 2. Conventional and ambulatory blood pressure, heart rate, side effects and metabolic changes were compared at the end of the run-in period on placebo, after 4 weeks on monotherapy and at the end of the 12-week period of active treatment. 3. Quinapril and atenolol reduced conventional blood pressure equally with substantial additional effect seen on combination therapy. The two regimens induced a significant decrease in ambulatory BP. However, the atenolol treated ambulatory hypertensive group experienced significantly greater decreases in diastolic blood pressure during 24 h, awake and sleep periods than did the quinapril group. 4. Adverse reactions were mild with both drugs except for severe Raynaud phenomenon in one patient in the atenolol group. Triglyceride levels were significantly increased with atenolol alone and in combination with hydrochlorothiazide. 5. Thus, within the limits of the dose ranges tested, quinapril and atenolol as single drugs or in combination with hydrochlorothiazide reduce significantly conventional and ambulatory blood pressure in moderate to severe hypertensives, but atenolol is more effective in reducing ambulatory diastolic blood pressure.
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PMID:Comparison of quinapril and atenolol as single drugs or in combination with hydrochlorothiazide in moderate to severe hypertensives, using automated ambulatory monitoring. 844 29

The effect of calcium channel blocker (CCB), amlodipine (5-10 mg/day) and angiotensin-converting enzyme (ACE) inhibitor, quinapril (10-40 mg/day) on ambulatory blood pressure (ABP), rheological and platelet function in hypertension were compared in this randomised double-blind placebo-controlled cross-over study. This study was preceded by 4 weeks placebo run-in period and the total duration of the study was 28 weeks. Casual and 24 h ABP, plasma renin activity (PRA) and plasma aldosterone (PA) concentration as well as metabolic and platelet function were determined before and at the end of each drug therapy. A total of 27 patients completed this study. Casual BP was significantly reduced after amlodipine or quinapril treatment, but there was no change in heart rate. Regarding the 24 h ABP, amlodipine produced a fall from 145 +/- 8/94 +/- 7 to 130 +/- 13/85 +/- 10 mm Hg (P < 0.001 for both SBP and DBP). Quinapril also caused a reduction from 144 +/- 10/94 +/- 7 to 134 +/- 12/88 +/- 8 mm Hg (P < 0.001 for both SBP and DBP). Neither amlodipine nor quinapril produce any significant change in heart rate. The level of 6-keto-prostaglandin Fl alpha (6-Keto-PGFl alpha) was increased from 36.8 +/- 4.4 to 45.1 +/- 2.5 pg/ml (P < 0.05) and no significant change of thromboxane B2(TXB2) was noted after amlodipine treatment. PRA was increased from 1.24 +/- 0.31 to 1.62 +/- 0.41 ng/ml/h (P < 0.05) after quinapril treatment. Other biochemical parameters were unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Comparison of amlodipine and quinapril on ambulatory blood pressure and platelet function in hypertension. 852 79

Chronic administration of NG-nitro-L-arginine methyl ester (L-NAME) induces a rise in blood pressure that is prevented by angiotensin I-converting enzyme inhibitors or angiotensin II receptor (type 1) blockade. Alterations in vascular reactivity in this model have not been extensively studied and could potentially be involved in the pathogenesis of L-NAME-induced hypertension. In the present work, we aimed to study the vascular reactivity and cGMP content of aortic ring segments isolated from Wistar rats treated for 3 weeks with L-NAME or L-NAME plus the converting enzyme inhibitor quinapril. Quinapril prevented the rise in blood pressure in L-NAME-treated rats although acetylcholine-induced dilation in aortic rings was suppressed and sodium nitroprusside-induced dilation was increased in both L-NAME- and L-NAME plus quinapril-treated rats. In isolated aortic ring segments, chronic L-NAME decreased the contractile response to K+ (125 mmol/L), phenylephrine, angiotensin II, the G protein stimulator AlF4-, and the protein kinase C activator phorbol dibutyrate. In contrast to the upregulated sodium nitroprusside-induced dilation, the contractile capacity of the aorta in response to angiotensin II, phenylephrine, AlF4-, K+, and phorbol dibutyrate was restored by quinapril. Aortic cGMP was lowered in rats treated with L-NAME (530 +/- 120 fmol/mg protein, n = 12, P < .05) and L-NAME plus quinapril (461 +/- 140 fmol/mg protein, n = 12, P < .05) compared with controls (1798 +/- 522 fmol/mg protein, n = 12). We hypothesize that the continuous nitric oxide blockade by L-NAME might attenuate a continuous endogenous relaxing tone and is associated with an upregulated endogenous vasoconstrictor tone in large arteries. Converting enzyme inhibition interfered more with the increased endogenous constrictor tone than with the decreased vasodilator tone in the wall of large arteries from L-NAME-treated rats.
Hypertension 1996 Sep
PMID:In vitro alteration of aortic vascular reactivity in hypertension induced by chronic NG-nitro-L-arginine methyl ester. 879 17

Blockade of the renin-angiotensin system (RAS) prevents the increase in blood pressure (BP) induced by chronic administration of NG-nitro L-arginine methyl ester (L-NAME) in rats. In the present study, we showed how a converting enzyme inhibitor can prevent the end-stage tissue damage due to chronic nitric oxide (NO) synthase blockade and thus improve the survival rate. Three experiments were performed. In the first, rats (n = 10) were given L-NAME (50 mg/kg) and 10 other rats were given L-NAME plus quinapril (10 mg/kg) starting 1 month after L-NAME administration. Ten untreated rats were used as controls. Rats were killed after 2 months, and the RAS, renal function, and renal morphology were analyzed. In the second experiment, a similar protocol was used, and function and morphological damage in renal slices and cervical medullary tissue were assessed after 4 months of L-NAME and 3 months of quinapril + L-NAME. In the third experiment, a similar protocol was used, but to establish survival curves, the animals were not killed. L-NAME significantly increased BP without causing any significnat changes in plasma renin activity (PRA) at 2 months. The aortic wall cyclic GMP content was significantly decreased, and the angiotensin-converting enzyme (ACE) activity was increased by L-NAME. Quinapril significantly reversed the high BP induced by L-NAME without changing the decrease in the aortic wall cyclic GMP. Two-month L-NAME treatment decreased renal function and damaged renal tissue. Quinapril prevented both proteinuria and morphological damage. Four-month L-NAME treatment induced renal end-stage damage and infarctions of the cervical medulla. Quinapril prevented this end-stage damage in the kidney and cervical medulla. Quinapril therefore prevented the increased mortality due to L-NAME. Hence, inhibition of ACE, despite its lack of effect on arterial wall cyclic GMP, does reverse the hypertension and prevent end-stage vascular damage induced by chronic L-NAME in target organs.
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PMID:Improved survival in rats administered NG-nitro L-arginine methyl ester due to converting enzyme inhibition. 879 48

A drug surveillance study was performed to determine the tolerance and safety of quinapril in the treatment of patients with stage 1 or 2 hypertension. The trial was noncomparative, open-label, uncontrolled, and nonrandomized. Patients with secondary hypertension, heart failure, other heart diseases, and other serious conditions were excluded. After a washout period of 2 weeks, 752 patients (316 men and 436 women) with diastolic blood pressure (DBP) between 90 and 115 mm Hg and systolic blood pressure (SBP) between 140 and 200 mm Hg were entered into the treatment phase. The mean age of patients (+/- SD) was 53.1 +/- 11.4 years. Patients initially received 10 mg/d quinapril for 4 weeks. For nonresponders, the dosage was titrated up to a maximum of 40 mg. Active treatment continued for 12 weeks. Initial blood pressures (mean +/- SD) were DBP, 102 +/- 6.1 mm Hg, and SBP, 163 +/- 14.4 mm Hg. Final blood pressures were DBP, 83 +/- 6.5 mm Hg, and SBP, 135 +/- 11.6 mm Hg. The response rate for the therapeutic goal (DBP < 90 mm Hg and SBP < 140 mm Hg, or a reduction in SBP > or = 20 mm Hg) was 67.1%; 41 patients did not complete the study. The most common adverse events were cough, headache, and dizziness; only 10 patients (1.3%) failed to complete the study because of adverse events. Quinapril, as used in current private clinical practice, is well tolerated and effective for the treatment of patients with stage 1 or 2 hypertension.
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PMID:Usefulness of low-dose, once-daily quinapril as monotherapy for patients with hypertension. 893 Apr 30


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