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(Hypertension. 1997;29:1314-1321.)
© 1997 American Heart Association, Inc.

Articles

Cyclosporine Impairs the Ability of Human Platelets to Mediate Vasodilation

Helgi J. Óskarsson; Timothy G. Hofmeyer; ; Maria Theresa Olivari

From The University of Iowa, Department of Internal Medicine, Iowa City, (H.J.O., T.G.H.) and the University of Nebraska Medical Center, Department of Internal Medicine, Section of Cardiology, Omaha (M.T.O.).

Correspondence to Helgi Óskarsson, MD, Department of Internal Medicine, Division of Cardiovascular Diseases, University of Iowa Hospitals and Clinics, 200 Hawkins Dr, Iowa City, IA 52242. E-mail helgi-oskarsson{at}uiowa.edu

Abstract Cyclosporine causes various platelet abnormalities. Whether it affects the ability of platelets to mediate vasodilation is unknown. Platelets were isolated from healthy volunteers and 13 heart transplant patients on cyclosporine. When perfused through preconstricted normal rabbit carotid arteries, activated platelets from transplant patients failed to cause vasorelaxation, whereas normal platelets produced significant vasodilation (-4.0±1.9% versus 30±3% [P<.0001] change in vessel diameter, respectively). When normal platelets were exposed to cyclosporine in vitro, they lost their ability to cause vasodilation in a dose- and time-dependent fashion. However, when activated and perfused through quiescent, N-nitro-L-arginine–pretreated arteries, platelets from transplant patients and normal platelets caused similar degrees of vasoconstriction. The amount of adenosine triphosphate in the supernatant from activated cyclosporine-exposed and control platelets was similar (1.7±0.4 versus 1.5±0.3 µmol/L [P=NS], respectively). However, concomitant perfusion of activated platelets from transplant patients impaired acetylcholine-mediated, endothelium-dependent vasodilation but perfusion of normal platelets did not. Although cyclosporine-exposed platelets showed an impaired ability to produce vasorelaxation, supernatant from the same platelets caused near normal vasodilation. Human platelets exposed to cyclosporine have an impaired ability to mediate vasodilation. This is not due to increased platelet-mediated vasoconstriction or a decrease in the release of platelet-derived nucleotides but rather to a short-acting compound released by cyclosporine-exposed platelets that interferes with endothelium-dependent vasodilation.

Key Words: cyclosporine • platelets • endothelium • vasoconstriction

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