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

被引:18
作者
Broeders, MAW
Tangelder, GJ
Slaaf, DW
Reneman, RS
Egbrink, MGAO
机构
[1] Maastricht Univ, Cardiovasc Res Inst Maastricht, Dept Physiol, NL-6200 MD Maastricht, Netherlands
[2] Maastricht Univ, Cardiovasc Res Inst Maastricht, Dept Biophys, NL-6200 MD Maastricht, Netherlands
[3] Free Univ Amsterdam, Inst Cardiovasc Res, Physiol Lab, Amsterdam, Netherlands
关键词
vessel wall injury; thromboembolism pathophysiology; nitric oxide; prostaglandins; wall shear rate;
D O I
10.1161/01.ATV.21.1.163
中图分类号
R5 [内科学];
学科分类号
1002 [临床医学]; 100201 [内科学];
摘要
It has been shown that NO and prostacyclin (prostaglandin I-2 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 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, 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-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 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.
引用
收藏
页码:163 / 169
页数:7
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