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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2002;22:680.)
© 2002 American Heart Association, Inc.

Thrombosis

Hypercholesterolemia Enhances Thromboembolism in Arterioles but Not Venules

Complete Reversal by L-Arginine

Martijn A.W. Broeders; Geert Jan Tangelder; Dick W. Slaaf; Robert S. Reneman; Mirjam G.A. oude Egbrink

From the Departments of Physiology (M.A.W.B., G.J.T., R.S.R., M.G.A.o.E.) and Biophysics (D.W.S.), CARIM, Maastricht University, Maastricht, the Netherlands. Dr Broeders is now at the Department of Internal Medicine, Rijnland Hospital, Leiderdorp, the Netherlands, and Dr Tangelder is now at the Laboratory for Physiology, ICAR-VU, Vrije Universiteit Medical Center, Amsterdam, the Netherlands.

Correspondence to M.G.A. oude Egbrink, PhD, Department of Physiology, Maastricht University, PO Box 616, 6200 MD Maastricht, Netherlands. E-mail M.oudeEgbrink{at}fys.unimaas.nl

We investigated in vivo the effect of cholesterol diet–induced hypercholesterolemia (HC) on thromboembolism in nonatherosclerotic rabbit mesenteric arterioles and venules (diameter 21 to 45 µm). After mechanical vessel wall injury, the ensuing thromboembolic reaction was studied by intravital videomicroscopy. A dramatic prolongation of embolization duration (median >600 seconds) was observed in the arterioles of the HC group compared with the arterioles of a normal chow–fed (NC) control group (142 seconds, P<0.0001); concomitantly, relative thrombus height increased (thrombus height/vessel diameter was 68% for the HC group and 58% for the NC group; P<0.05). By contrast, in venules, cholesterol did not affect embolization duration (42 seconds for HC group, 34 seconds for NC group) and thrombus height (66% for HC group, 64% for NC group). Furthermore, the role of endothelial NO synthesis was studied. In arterioles, stimulation of endogenous NO synthesis through mesenteric superfusion of L-arginine (1 mmol/L) completely reversed cholesterol-enhanced embolization (152 seconds) but did not influence thrombus height (63%). L-Arginine had no effect in venules of the HC group (51 seconds) and nor in the arterioles and venules of the NC group (177 seconds for arterioles, 43 seconds for venules). This study indicates that hypercholesterolemia selectively enhances thrombus formation and embolization in arterioles but not in venules and that stimulation of endogenous NO production antagonizes this enhancement of arteriolar thromboembolism.

Key Words: vessel wall injury • in vivo thromboembolism • nitric oxide • cholesterol

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