Kidney Blood Press
Res. 2005;28(2):111-6. Epub 2005 Mar 1.
Comparison of the effects of quinapril and losartan on carotid
artery intima-media thickness in patients with mild-to-moderate arterial
hypertension.
Uchiyama-Tanaka Y, Mori Y, Kishimoto N, Fukui M, Nose A, Kijima
Y, Yamahara H, Hasegawa T, Kosaki A, Matsubara H, Iwasaka T.
Department of Medicine II, Kansai Medical University, Osaka, Japan.
BACKGROUND: Ultrasonographic evidence of increased carotid intima-media
thickness (IMT) is known to be associated with generalized atherosclerosis.
Therapeutic blockade of the renin-angiotensin system (RAS) with angiotensin-converting
enzyme (ACE) inhibitors reportedly reduces carotid IMT in humans. However,
there has been no head-to-head comparison of the effects of ACE inhibitor
and angiotensin receptor blocker (ARB), a newer type of RAS inhibitor,
on carotid IMT. METHODS: 57 hypertensive patients were randomly assigned
to treatment with one of two antihypertensive drugs: ACE inhibitor (quinapril;
n = 25, group Q) or ARB (losartan; n = 18, group L). RESULTS: After 1
year of treatment, a similar decrease in mean blood pressure was observed
in all groups. Carotid IMT was decreased significantly in group Q (10%
decrease, p < 0.05) but did not change in group L. There were no significant
changes in other atherosclerotic factors between these two groups. Conclusion:
Our findings suggest that the antiatherosclerotic effect of quinapril
is more potent than that of losartan in hypertensive patients. This effect
appears unrelated to the drug's antihypertensive action or to traditional
atherosclerotic factors.
Am J Hypertens. 2005 Apr;18(4 Pt 1):557-65.
Potential role of angiotensin-converting enzyme inhibitors and
statins on early podocyte damage in a model of type 2 diabetes mellitus,
obesity, and mild hypertension.
Blanco S, Vaquero M, Gomez-Guerrero C, Lopez D, Egido J, Romero
R.
Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona,
Spain.
BACKGROUND: Experimental findings suggest that the obese Zucker rat (OZR)
is a model of type 2 diabetes-related nephropathy with several metabolic
abnormalities. However, the exact mechanisms by which these factors cause
early glomerulosclerosis and proteinuria remain unclear. Furthermore,
structural abnormalities and regulation of podocytes have recently emerged
as prominent underlying factors in proteinuria. The aim of this study
was to evaluate the potential role of angiotensin-converting enzyme inhibitors
and statins on early podocyte damage in an experimental model of type
2 diabetes mellitus. METHODS: We used OZR to evaluate some of the pathogenic
mechanisms and the effects of two drugs, an angiotensin-converting enzyme
(ACE) inhibitor (quinapril) and a statin (atorvastatin), involved in the
development of proteinuria and especially podocyte damage. We studied
glomerular and tubulointerstitial injury by assessing inflammation mediators
(murine monoclonal antibody against CD68 [ED1+], interleukin-8 [IL-8],
interferon-gamma-inducible protein 10 [IP-10]) and podocyte damage markers
using desmin staining and electron microscopy. RESULTS: Glomerular lesions
were correlated with cholesterol (r = 0.676), proteinuria (r = 0.804),
triglycerides (r = 0.593), insulin (r = 0.345), creatinine (r = 0.266),
and glucose (r = 0.245). In addition, podocytes from OZR showed positive
staining for desmin. Use of the ACE inhibitor quinapril normalized proteinuria,
cholesterol levels, glomerular lesions, and podocyte morphology. In contrast,
atorvastatin ameliorated but did not normalize renal damage, with a partial
reduction in desmin staining and podocyte morphology. Treatment with both
drugs resulted in only a slight reduction in IL-8 and IP-10 in the tubulointerstitium.
CONCLUSIONS: In the OZR, cholesterol was an important determinant of renal
injury. Most notably, glomerulosclerosis in the OZR Is characterized by
early podocyte damage and tubulointerstitial injury. In addition, our
findings showed that quinapril primarily normalized podocyte morphology,
whereas atorvastatin ameliorated renal lesions through the diminution
of lipids and by its lipid-independent pleiotropic effect.
Naunyn Schmiedebergs Arch Pharmacol. 2004 Nov 10;
Quinapril effects on resistance artery structure and function
in hypertension.
Yang L, Gao YJ, Lee RM.
Smooth Muscle Research Programme and Department of Anaesthesia, McMaster
University, L8N 3Z5, Hamilton, ON, Canada.
The effects of chronic treatment with quinapril on blood pressure, vascular
reactivity and structure of resistance arteries were examined in adult,
male spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats. SHR
and WKY at 15 weeks of age were treated with quinapril (10 mg/kg per day)
for 10 weeks. Structural changes in the mesenteric arteries were measured
by optical sectioning with confocal microscopy and in renal arteries by
light microscopic measurements. Apoptotic cells in the mesenteric vessel
wall were identified using the terminal deoxynucleotide transferase-mediated
dUTP-nick end-labelling (TUNEL) method. The response of mesenteric arteries
to noradrenaline, electrical stimulation, acetylcholine and sodium nitroprusside
was studied using a pressure myograph system. Treatment with quinapril
significantly lowered systolic blood pressure and ventricular weight in
both SHR and WKY. It reduced wall thickness and medial volume in mesenteric
arteries from SHR and WKY and media-to-lumen ratio in interlobular arteries
of SHR. It also decreased the number of smooth muscle layers in SHR and
increased the number of apoptotic smooth muscle cells in both SHR and
WKY. In addition, treatment normalized the augmented contractile responses
and improved the impaired relaxation response of SHR mesenteric arteries
to the level of WKY. We conclude that treatment with quinapril lowered
blood pressure and improved cardiac and vessel structure and vessel function.
An increase in apoptotic process of medial smooth muscle cells is one
of the mechanisms underlying the vascular structural improvement.
Rheumatology (Oxford). 2004 Sep 7;
The non-thiol angiotensin-converting enzyme inhibitor quinapril
suppresses inflammatory arthritis.
Dalbeth N, Edwards J, Fairchild S, Callan M, Hall FC.
Division of Medicine, Imperial College London, London, UK; MRC Human
Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe
Hospital, Oxford, UK.
Objectives. In addition to its vasoactive effects, angiotensin II has proinflammatory properties. Angiotensin-converting enzyme (ACE) inhibitors reduce the production of angiotensin II and could therefore act as anti-inflammatory agents. Here we investigated the capacity of the ACE inhibitor quinapril to modulate inflammatory arthritis. Methods. We studied the effect of quinapril on disease activity in mice with collagen-induced arthritis (CIA). Mice received oral quinapril (10 mg/kg/day) at the time of arthritis induction (prophylaxis protocol) or at the onset of mild arthritis (therapy protocol). Concentrations of immunoglobulin G (IgG) subtypes specific for bovine Type II collagen and TNF-alpha were measured by enzyme-linked immunoassay. Results. Quinapril significantly diminished the activity of CIA when given as prophylaxis or therapy (prophylaxis protocol, P<0.001; therapy protocol P = 0.002). Antigen-specific IgG2a antibodies were reduced by 52% (P = 0.02) in the quinapril prophylaxis protocol. Suppression of arthritis by quinapril was associated with reduced articular expression of TNF-alpha by 68% (P = 0.01) in the prophylaxis protocol and 27% (P = 0.06) in the therapy protocol. Quinapril therapy also inhibited expression of splenocyte TNF-alpha production following lipopolysaccharide (LPS) in vitro stimulation by 59% (P = 0.02). In parallel human in vitro experiments, ACE inhibition suppressed LPS-stimulated production of TNF-alpha by monocytes. In order to confirm that the action of quinapril occurred predominantly through suppression of angiotensin II, parallel experiments with the angiotensin receptor antagonist candesartan cilexetil demonstrated that this agent also inhibited disease activity in CIA. Conclusions. These data suggest that angiotensin II is a mediator of chronic inflammation and that ACE inhibition may have therapeutic effects in human inflammatory arthritis.
Clin Cardiol. 2004 Aug;27(8):480-4.
Effect of quinapril on the attenuated heart rate recovery of type
2 diabetic subjects without known coronary artery disease.
Sipahi I, Tekin G, Yigit Z, Guzelsoy D, Guven O.
Department of Cardiology, Cardiology Institute, Istanbul University,
Istanbul, Turkey.
BACKGROUND: Heart rate (HR) recovery at 1 min is a measure of the vagal reactivation that occurs after cessation of exercise. Despite ample evidence about the association of attenuated HR recovery with increased mortality, pharmacologic modification of this predictor has not been shown. On the other hand, angiotensin-converting enzyme (ACE) inhibitors are known to have vagomimetic activity. HYPOTHESIS: We hypothesized that ACE inhibition would increase HR recovery in a group of subjects known to have reduced HR recovery, namely diabetics. METHODS: Maximal treadmill exercise stress test was performed in 31 type 2 diabetic and 31 nondiabetic male subjects with similar age, body mass index, and hypertensive status. None of the subjects had known heart disease or evidence of myocardial ischemia during the test. The diabetic subjects, after 2 weeks of treatment with quinapril, underwent a second exercise test. A third test was performed 2 to 3 weeks after cessation of quinapril treatment. RESULTS: At baseline, despite similar exercise capacity, the diabetics had a lower HR recovery at 1 min than nondiabetics (25 +/- 8 vs. 31 +/- 8 beats/min, p < 0.01). Quinapril significantly increased HR recovery at 1 min in diabetics (25 +/- 8 beats/min at baseline vs. 28 +/- 8 beats/min with quinapril vs. 25 +/- 7 beats/min off-therapy, p < 0.01 by analysis of variance). CONCLUSIONS: The attenuated HR recovery of type 2 diabetics can be improved by quinapril. Whether the improvement in HR recovery with ACE inhibition can lead to decreased mortality is currently unknown.
Diabetes Care. 2004 Jul;27(7):1712-5.
Quinapril, an ACE inhibitor, reduces markers of oxidative stress
in the metabolic syndrome.
Khan BV, Sola S, Lauten WB, Natarajan R, Hooper WC, Menon RG,
Lerakis S, Helmy T.
Division of Cardiology, Emory University School of Medicine, Atlanta,
GA 30303, USA.
OBJECTIVE: Patients with the metabolic syndrome often have abnormal levels of proinflammatory and pro-oxidative mechanisms within their vasculature. We sought to determine whether the ACE inhibitor quinapril regulates markers of oxidative stress in the metabolic syndrome. RESEARCH DESIGN AND METHODS: Forty patients with the metabolic syndrome were randomized in a double-blind manner to either the ACE inhibitor quinapril (20 mg/day) or matching placebo for 4 weeks. Serum markers of vascular oxidative stress were measured. RESULTS: After 4 weeks of therapy, serum 8-isoprostane was reduced by 12% in the quinapril group when compared with placebo (quinapril, 46.7 +/- 1.0; placebo, 52.7 +/- 0.9 pg/ml; P = 0.001). Erythrocyte superoxide dismutase activity increased 35% in the quinapril group when compared with placebo (quinapril, 826.3 +/- 17.1; placebo, 612.3 +/- 6.9 units/g Hb; P < 0.001). In addition, lag time to oxidation of LDL, a marker of oxidative stress, was increased by 48% in the quinapril group when compared with placebo (quinapril 89.2 +/- 9.2 vs. placebo 60.1 +/- 12.3 min; P < 0.001). Therapy with quinapril was well tolerated. CONCLUSIONS: The addition of the ACE inhibitor quinapril reduces markers of vascular oxidative stress and may attenuate the progression of the pathophysiology seen in the metabolic syndrome.
Pharmacology. 2004 Jul;71(3):157-61.
Comparative effects of quinapril with enalapril in rats with heart
failure.
Watanabe K, Ma M, Wen J, Tachikawa H, Kodama M, Aizawa Y, Yamaguchi
K, Takahashi T.
Department of Clinical Pharmacology, Niigata University of Pharmacy
and Applied Life Sciences, Niigata City, Japan.
The cardioprotective properties of angiotensin-converting enzyme (ACE) inhibitors, quinapril and enalapril were studied in a rat model of heart failure. Seventy-five rats were divided into five groups and administered quinapril or enalapril at 2 and 20 mg/kg/day (groups Q2, Q20, E2 and E20) or vehicle alone (group V, all groups n = 15). Although both ACE inhibitors improved survival rate and ventricular function in a dose-dependent manner, the left ventricular end-diastolic pressure and expression level of transforming growth factor-beta1 mRNA were the lowest in group Q20. These results suggest that quinapril may confer greater protection than enalapril against injury from the renin-angiotensin system in heart failure. Copyright 2004 S. Karger AG, Basel
Am Heart J. 2004 Apr;147(4):662-8.
Long-term effects of quinapril with high affinity for tissue angiotensin-converting
enzyme after coronary intervention in Japanese.
Otsuka M, Yamamoto H, Okimoto T, Dohi Y, Mito S, Gomyo Y, Fujii
T, Matsuura W, Hirai Y, Kohno N.
Department of Molecular and Internal Medicine, Division of Clinical
Medical Science, Programs for Applied Biomedicine, Graduate School of
Biomedical Sciences, Hiroshima University, Hiroshima, Japan.
BACKGROUND: Angiotensin-converting enzyme inhibitors have been shown experimentally to prevent restenosis after balloon injury. We previously reported that quinapril reduced the 6-month restenosis (percent diameter stenosis >or=50%) rate after percutaneous coronary intervention (PCI). However, it was not established whether this favorable outcome was maintained for longer periods. METHODS: This study was a prospective, randomized, open, and non-placebo controlled trial. Patients with coronary artery disease were enrolled after successful coronary balloon angioplasty or stenting. Two hundred and fifty-three patients were randomly assigned to the quinapril (10-20 mg per day) or control groups. The major clinical end points included death, myocardial infarction, cerebrovascular accident, or revascularization (either coronary artery bypass grafting or repeat PCI). These were tabulated according to the intention-to-treat principle. RESULTS: Long-term follow-up was available with a median of 4.8 (interquartile range 4.2-5.1) years after the procedure. The incidence of combined end points of mortality and morbidity (myocardial infarction and cerebrovascular accident) in the quinapril group was lower than that in the control group (6.1% vs 14.8%; relative risk [RR] 0.42, 95% CI 0.18-0.96, P =.033). The overall incidence of end-point events in patients with quinapril also occurred less frequently (29.8% vs 46.7%; RR 0.58, 95% CI 0.38-0.86, P =.007). CONCLUSIONS: These clinical outcomes show that the benefit of quinapril in patients following PCI is maintained for 4 years.
J Am Coll Cardiol. 2003 Dec 17;42(12):2049-59.
Effects of angiotensin-converting enzyme inhibition on transient
ischemia: the Quinapril Anti-Ischemia and Symptoms of Angina Reduction
(QUASAR) trial.
Pepine CJ, Rouleau JL, Annis K, Ducharme A, Ma P, Lenis J, Davies
R, Thadani U, Chaitman B, Haber HE, Freedman SB, Pressler ML, Pitt B;
QUASAR Study Group.
University of Florida College of Medicine, Division of Cardiovascular
Medicine, Gainesville, Florida 32610-0277, USA.
OBJECTIVES: We sought to determine whether angiotensin-converting enzyme inhibition (ACE-I) (i.e., quinapril) prevents transient ischemia (exertional and spontaneous) in patients with coronary artery disease (CAD). BACKGROUND: It is known that ACE-I reduces the risk of death, myocardial infarction (MI), and other CAD-related outcomes in high-risk patients. Numerous studies have confirmed that ACE-I improves coronary flow and endothelial function. Whether ACE-I also decreases transient ischemia is unclear, because no studies have been adequately designed or sufficiently powered to evaluate this issue. METHODS: Using a randomized, double-blinded, placebo-controlled, multicenter design, we enrolled 336 CAD patients with stable angina. None had uncontrolled hypertension, left ventricular (LV) dysfunction, or recent MI, and all developed electrocardiographic (ECG) evidence of ischemia during exercise. They were randomly assigned to one of two groups: 40 mg/day quinapril (n = 177) or placebo (n = 159) for 8 weeks. Patients then entered an additional eight-week treatment phase to examine the full dose range. Those assigned to 40 mg quinapril continued that dose and those assigned to placebo were titrated to 80 mg/day. Treadmill testing, the Seattle Angina Questionnaire, and ambulatory ECG monitoring were used to assess responses at baseline and at 8 and 16 weeks. RESULTS: The groups did not differ significantly at entry or in terms of indexes assessing myocardial ischemia at 8 or 16 weeks of treatment. In this low-risk population, ACE-I was not associated with serious adverse events. CONCLUSIONS: Our findings suggest short-term ACE-I in CAD patients without hypertension, LV dysfunction, or acute MI is not associated with significant effects on transient ischemia.
Mol Cell Biochem. 2003 Sep;251(1-2):77-82.
Quinapril inhibits progression of heart failure and fibrosis in
rats with dilated cardiomyopathy after myocarditis.
Juan W, Nakazawa M, Watanabe K, Ma M, Wahed MI, Hasegawa G, Naito
M, Yamamoto T, Fuse K, Kato K, Kodama M, Aizawa Y.
Department of Clinical Pharmacology, Niigata University of Pharmacy
and Applied Life Sciences, Niigata, Japan.
The cardioprotective properties of quinapril, an angiotensin-converting
enzyme inhibitor, were studied in a rat model of dilated cardiomyopathy.
Twenty-eight days after immunization of pig cardiac myosin, four groups
rats were given 0.2 mg/kg (Q0.2, n = 11), 2 mg/kg (Q2, n = 11) or 20 mg/kg
(Q20, n = 11) of quinapril or vehicle (V, n = 15) orally once a day. After
1 month, left ventricular end-diastolic pressure (LVEDP), +/- dP/dt, area
of myocardial fibrosis, and myocardial mRNA expression of transforming
growth factor (TGF)-beta1, collagen-III and fibronectin were measured.
Four of 15 (27%) rats in V and two of 11 (18%) in Q0.2 died. None of the
animals in Q2 or Q20 died. The LVEDP was higher and +/- dP/dt was lower
in V (14.1 +/- 2.0 mmHg and +2409 +/- 150/-2318 +/- 235 mmHg/sec) than
in age-matched normal rats (5.0 +/- 0.6 mmHg and +6173 +/- 191/-7120 +/-
74 mmHg/ sec; all p < 0.01). After quinapril treatment, LVEDP was decreased
and +/- dP/dt was increased in a dose-dependent manner (10.8 +/- 1.8 mmHg
and +3211 +/- 307/-2928 +/- 390 mmHg/sec in Q0.2, 9.4 +/- 1.5 mmHg and
+2871 +/- 270/-2966 +/- 366 mmHg/sec in Q2, and 6.6 +/- 1.5 mmHg, and
+3569 +/- 169/-3960 +/- 203 mmHg/sec in Q20). Increased expression levels
of TGF-beta1, collagen-III and fibronectin mRNA in V were reduced in Q20.
Quinapril improved survival rate and cardiac function in rats with dilated
cardiomyopathy after myocarditis. Furthermore, myocardial fibrosis was
regressed and myocardial structure returned to nearly normal in animals
treated with quinapril.
