765-5 Platelet Inhibitory Effect of Endothelium-derived Relaxing Factor in the Human Coronary Circulation

Abstract

Endothelium-derived relaxing factor (EDAF) inhibits platelet activation by increasing platelet cyclic GMP content. In the human coronary circulation the vasodilator effect of EDRF released abluminally from the endothelium is well described, but the effects of luminal release of EDRF on platelets is unknown. Furthermore, whether decreased vasodilator responses to agents that stimulate EDRF release are also associated with an abnormal platelet response is unknown. We therefore studied the effects of intracoronary acetylcholine (ACh), which stimulates the endothelial release of EDRF, on blood flow and platelet cGMP content in 14 patients with agiographically normal coronary arteries undergoing cardiac catheterization. Seven patients received sodium nitroprusside (SNP) infusions. Blood flow was derived from Doppler flow velocity, and diameter was measured by quantitative angiography. Simultaneous samples were drawn from the great cardiac vein for measurement of platelet cGMP content by radioimmunoassay. During ACh infusion (30 μg/min) there was a transient increase in both coronary flow 138 ± 25% (mean ± SEM, p < 0.01) and platelet cGMP content (34 ± 13%. p < 0.01), that returned to baseline (both p < 0.01). Epicardial diameter responses to ACh were heterogenous: seven patients showed constriction (-7 ± 2%) and seven showed dilatation (11 ± 2%). Changes in platelet cGMP content and epicardial diameter paralleled each other: in patients with dilatation, ACh increased cGMP content significantly (54 ± 22%, P < 0.02), whereas in those with constriction the change in cGMP was insignificant (14 ± 8%, P = NS). During SNP infusion (40 μ g/min) flow increased by 127 ± 23% and cGMP content by 226 ± 55% (p < 0.02). 1) luminal release of EDRF in the human coronary circulation causes an increase in platelet cGMP content; 2) this effect is less evident in patients with impaired endothelial-mediated vasodilation. Failure of this platelet inhibitory effect in patients with atherosclerosis and endothelial dysfunction may contribute to their increased susceptibility to thrombotic vascular events.