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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2001;21:163.)
© 2001 American Heart Association, Inc.

Thrombosis

Endogenous Nitric Oxide and Prostaglandins Synergistically Counteract Thromboembolism in Arterioles but Not in Venules

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., R.S.R., M.G.A. oude E.) and Biophysics (D.W.S.), Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, the Netherlands; and the Laboratory for Physiology (G.-J.T.), Institute for Cardiovascular Research, Free University, Amsterdam, the Netherlands.

Correspondence to M.G.A. oude Egbrink, PhD, Department of Physiology, Cardiovascular Research Institute Maastricht, Maastricht University, Universiteitssingel 50, PO Box 616, 6200 MD Maastricht, the Netherlands. E-mail m.oudeegbrink{at}fys.unimaas.nl

Abstract—It has been shown that NO and prostacyclin (prostaglandin I₂) from cultured endothelium synergistically inhibit blood platelet aggregation in vitro. However, it is unknown whether this synergism is also effective in the inhibition of thromboembolism in vivo and, if it is, whether it differs between vessel types. Therefore, the effect of endogenous NO and prostacyclin, in combination or alone, on thromboembolism was studied in an in vivo model. Thromboembolism was induced by micropipette puncture of rabbit mesenteric arterioles and venules (diameter 18 to 40 µm). In addition, the influence of wall shear rate was analyzed. In arterioles, the combined inhibition of NO synthase (N^G-nitro-L-arginine [L-NA] 0.1 mmol/L; local superfusion) and of cyclooxygenase (aspirin [ASA] 100 mg/kg IV) resulted in a pronounced, significant prolongation of embolization duration (median >600 seconds) compared with control (median 153 seconds) or treatment with either L-NA (234 seconds) or ASA (314 seconds). This combined effect of L-NA+ASA was greater than the sum of the individual effects of L-NA and ASA. In contrast, in venules L-NA+ASA had no additional effect on embolization duration (209 seconds) compared with the effect of L-NA alone (230 seconds); ASA alone had no effect (122 seconds; control 72 seconds). Interestingly, only in the L-NA+ASA arterioles did embolization correlate positively with wall shear rate (r_s=0.687; P=0.028). In conclusion, this study indicates that in arterioles, but not in venules, endogenous NO and prostaglandins synergistically counteract ongoing thromboembolism after vessel wall injury and that the combination of endogenous NO and prostaglandins appears to protect against enhancement of arteriolar thromboembolism by wall shear rate.

Key Words: vessel wall injury • thromboembolism pathophysiology • nitric oxide • prostaglandins • wall shear rate

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