Cardioprotective effects of citrulline in ischemia/reperfusion injury via a non-nitric oxide-mediated mechanism

The effects of L-citrulline, the byproduct of nitric oxide (NO) synthesis, and its stereoisomer D-citrulline were studied in a polymorphonuclear leuko cyte (PMN)-dependent isolated perfused rat heart model consisting of 20 min of global ischemia and 45 min of reperfusion. Ischemic hearts reperfused w ith either D- or L-citrulline (20 nM) exhibited a marked presentation of le ft ventricular developed pressure and of maximal rate of development of lef t ventricular developed pressure, compared to hearts perfused without eithe r D- or L-citrulline (both p < 0.001). In addition, both D- and L-citrullin e significantly attenuated PMN accumulation in die post-reperfused myocardi um from 288 +/- 33 PMNs/mm(2) in untreated hearts to 89 +/- 10 and 76 +/- 6 PMNs/mm(2), respectively (both p < 0.001). In isolated rat aortic rings, n either D- or. L-citrulline induced any vasodilation or release of nitric ox ide from the vascular endothelium. However expression of P-selectin on the coronary vascular endothelium was markedly attenuated in hearts perfused wi th either. D- or L-citrulline compared to ischemic-reperfused hearts withou t citrulline (both p < 0.001). These results provide evidence that D- or L- citrulline significantly attenuates PMN-induced cardiac contractile dysfunc tion in the isolated perfused rat hear subjected to ischemia/reperfusion Vi a a non-NO-mediated mechanism. (C) 2000 Prous Science. All rights reserved.