Nitric oxide synthase inhibition is associated with decreased survival of cardiac allografts in the rat.

Nitric oxide is a biological mediator that regulates blood vessel wall tonus, enhances macrophage cytotoxicity, and inhibits cellular immune reactivity. Primary acute rejection is associated with increased intragraft production of NO but it is unknown whether this delays or enhances the loss of graft function. The aim of the current study was to determine the effect of L-NAME, a nitric oxide synthase inhibitor, on the course and histopathology of rat cardiac allografts with primary acute rejection. L-NAME decreased the graft survival time from 9.4+/-1.5 to 6.9+/-0.3 days; the histopathology at asystole showed predominantly ischemic necrosis. L-NAME combined with antihypertensive drugs restored the rejection time (from 8.6+/-0.4 to 14.2+/-3.2 days) and resulted in an acute rejection pattern. We conclude that blocking of nitric oxide formation during acute rejection of a vascularized cardiac graft results in a decreased graft survival time and ischemic graft necrosis, very likely secondary to unopposed vasoconstriction.