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Inhibition of Arterial Thrombogenesis by Quinapril but Not Losartan

Departments of Medicine, Pathology, and Physiology, University of Florida, College of Medicine and the VA Medical Center, Gainesville, Florida

Dayuan Li

Departments of Medicine, Pathology, and Physiology, University of Florida, College of Medicine and the VA Medical Center, Gainesville, Florida

Dani S. Zander

Departments of Medicine, Pathology, and Physiology, University of Florida, College of Medicine and the VA Medical Center, Gainesville, Florida

M. Ian Phillips

Departments of Medicine, Pathology, and Physiology, University of Florida, College of Medicine and the VA Medical Center, Gainesville, Florida

Jawahar L. Mehta

Departments of Medicine, Pathology, and Physiology, University of Florida, College of Medicine and the VA Medical Center, Gainesville, Florida

The cardioprotective effect of angiotensin converting enzyme (ACE) inhibitors and angio tensin type I (AT1) receptor blockers may relate to their antithrombotic effect. We determined the differential effects of the ACE inhibitor quinapril and the AT1 receptor blocker losartan on arterial thrombus formation in the rat. Sprague-Dawley rats were fed regular chow or chow mixed with low-dose quinapril (0.6 mg/kg/day), high-dose quinapril (1.2 mg/kg/day), or losartan (10 mg/kg/day) for 15 days. Abdominal aorta was exposed and wrapped with Whatman paper impregnated with 29% FeCl₃ (ferric chloride). Time to occlusive thrombus formation and weight of the thrombus were recorded. Aortic superoxide anion generation, platelet aggregation, plasma angiotensin II levels, and morphology of the thrombus were also examined. Both losartan and quinapril caused similar reductions in arterial pressure. Losartan did not affect the time to thrombus formation, whereas quinapril (both low and high doses) delayed the time to thrombus formation (P < .01 vs control). Weight of the thrombus was similar in all groups of rats. Platelet aggregation was inhibited by approximately 50% in both quinapril- and losartan-treated rats. The high-dose quinapril-treated rats showed markedly reduced vascular superoxide anion generation compared with the control rats (P < .05). Plasma angiotensin II levels were unaffected by quinapril treatment but were elevated 7-fold in losartan-treated rats (P < .001 vs. control rats). The thrombi in the control rats consisted of platelet aggregates, fibrin, and red blood cells. The intravascular platelet aggregates were much smaller in the quinapril-treated rats (P < .05 vs. control), but were similar in control and losartan-treated rats. In conclusion, quinapril but not losartan prolongs time to arterial throm bus formation and results in smaller platelet aggregates in the thrombus. Both quinapril and losartan decrease platelet aggregation, but only quinapril decreases superoxide anion gen eration. This effect on superoxide anion generation as well as mechanisms other than AT 1 receptor blockade may underlie the salutary effect of quinapril on arterial thrombogenesis.

Key Words: ACE inhibition • losartan • quinapril • superoxide anions • thrombosis.

Journal of Cardiovascular Pharmacology and Therapeutics, Vol. 5, No. 2, 121-127 (2000)
DOI: 10.1053/XV.2000.5490


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