CYCLIC-GMP BUT NOT CYCLIC-AMP PREVENTS RENAL PLATELET ACCUMULATION AFTER ISCHEMIA-REPERFUSION IN ANESTHETIZED RATS

Platelets have been implicated in the pathophysiology of ischemia-repe rfusion injury. In this study, antiplatelet effects of cyclic GMP (cGM P)- and cyclic AMP (cAMP)-mediated agents were evaluated in renal isch emia in pentobarbital-anesthetized rats. Renal ischemia was induced by unilateral occlusion of the left renal artery (40 min) followed by re perfusion (30 min) with the contralateral kidney serving as control. ( 111)Indium-labeled platelets, drugs or vehicle were administered 30 mi n before induction of renal ischemia. Occlusion of the left renal arte ry for 20, 40 or 60 min resulted in a 100, 300 and 600% increase (over contralateral right kidney) in the platelet-associated (111)indium ac tivity in the ischemic kidney. In all subsequent studies the kidney wa s occluded for 40 min to test the antiplatelet activity of individual agents. 8-Br-cGMP (0.1 and 0.3 mg/kg/min i.v.), zaprinast (0.1 mg/kg/m in i.v.) and sodium nitroprusside (0.003 and 0.01 mg/kg/min i.v.) sign ificantly attenuated platelet accumulation in renal ischemia, whereas 8-Br-cAMP (0.3 mg/kg/min i.v.) or milrinone(0.1 mg/kg i.v. bolus, plus 0.01 mg/kg/min) did not. Minoxidil (0.01 and 0.03 mg/kg/min i.v.), a vasodilator which produced equihypotensive effects as the cGMP-mediate d agents, and milrinone failed to prevent platelet accumulation. These results demonstrate that modulation of the platelet function by cGMP agents can be dissociated from their blood pressure lowering effects. cGMP is known to inhibit both platelet adhesion and aggregation, where as cAMP is only active against aggregation. The present findings provi de further evidence that cGMP-mediated drugs may afford effective anti platelet action in an in vivo model of ischemia-reperfusion injury.