EXOGENOUS NITRIC-OXIDE PREVENTS ENDOTOXIN-INDUCED GLOMERULAR THROMBOSIS IN RATS

Nitric oxide (NO) synthesized from L-arginine is an endogenous vasodil ator and inhibitor of platelet adhesion and aggregation. Gram-negative lipopolysaccharide (LPS) can induce NO synthesis, which may mediate t he pathophysiologic effects of endotoxemia. In addition, our previous studies suggested that LPS-induced NO may protect against thrombosis i n rats. In the present study, male Sprague-Dawley rats given LPS (0.1 mg/kg) i.p. increased their urinary excretion of NO2 + NO3 (stable end -products of NO) by 4.3-fold. Rats given 10 mu g/kg/hr i.v. of nitrogl ycerin (GTN), an exogenous NO donor, showed a similar increase. L-NAME , an inhibitor of NO synthesis, abrogated the increase in urinary NO2 + NO3 in LPS-treated rats but not in rats given GTN. Glomerular thromb osis developed in rats given LPS + L-NAME (thrombosis score = 3.02 +/- 0.4), while those given LPS + L-NAME + GTN were largely protected (th rombosis score = 1.37 +/- 0.5, P < 0.05). Atrial natriuretic peptide ( ANP), an NO-independent vasodilator, neither increased urinary NO2 + N O3 nor prevented glomerular thrombosis (thrombosis score = 2.68 +/- 0. 5, NS). Hydralazine, another vasodilator without effects on NO or plat elets, also failed to prevent glomerular thrombosis in rats given LPS + L-NAME. We conclude that in endotoxemia, the antithrombogenic proper ties of endogenously synthesized NO are important in preventing alomer ular thrombosis. The exogenously NO donor, GTN, can substitute for the antithrombogenic effect of endogenous NO. Clinically, administration of NO synthesis inhibitors to treat endotoxic shock may need to be com bined with concomitant administration of exogenous NO donors to preven t microvascular thrombosis.