Endogenous nitric oxide and prostaglandins synergistically counteract thromboembolism in arterioles but not in venules

It has been shown that NO and prostacyclin (prostaglandin I-2 from cultured endothelium synergistically inhibit blood platelet aggregation in vitro. H owever, it is unknown whether this synergism is also effective in the inhib ition of thromboembolism in vivo and, if it is, whether it differs between vessel types. Therefore, the effect of endogenous NO and prostacyclin, in c ombination or alone, on thromboembolism was studied in an in vivo model. Th romboembolism was induced by micropipette puncture of rabbit mesenteric art erioles and venules (diameter 18 to 40 mum). In addition, the influence of wall shear rate was analyzed. In arterioles, the combined inhibition of NO synthase (NC-nitro-L-arginine [L-NA] 0.1 mmol/L; local superfusion) and of cyclooxygenase (aspirin [ASA] 100 mg/kg IV) resulted in a pronounced, signi ficant prolongation of embolization duration (median >600 seconds) compared with control (median 153 seconds) or treatment with either L-NA (234 secon ds) 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-NAS ASA had no additional effect on embolization duration (209 seconds) compared with the effect of L-NA alone (230 seconds); ASA alone had no effe ct (122 seconds; control 72 seconds). Interestingly, only in the L-NA+ASA a rterioles did embolization correlate positively with wall shear rate (r(s)= 0.687; P=0.028). In conclusion, this study indicates that in arterioles, bu t not in venules, endogenous NO and prostaglandins synergistically countera ct ongoing thromboembolism after vessel wall injury and that the combinatio n of endogenous NO and prostaglandins appears to protect against enhancemen t of arteriolar thromboembolism by wall shear rate.