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 leukocyte (PMN)-dependent isolated perfused rat heart model consisting of 20 min of global ischemia and 45 min of reperfusion. Ischemic hearts reperfused with either D- or L-citrulline (20 nM) exhibited a marked preservation of left ventricular developed pressure and of maximal rate of development of left ventricular developed pressure, compared to hearts perfused without either D- or L-citrulline (both p < 0.001). In addition, both D- and L-citrulline significantly attenuated PMN accumulation in the post-reperfused myocardium from 288 Â± 33 PMNs/mm2 in untreated hearts to 89 Â± 10 and 76 Â± 6 PMNs/mm2, respectively (both p < 0.001). In isolated rat aortic rings, neither D- or L-citrulline induced any vasodilation or release of nitric oxide from the vascular endothelium. However, expression of P-selectin on the coronary vascular endothelium was markedly attenuated in hearts perfused with either D- or L-citrulline compared to ischemic-reperfused hearts without citrulline (both p < 0.001). These results provide evidence that D- or L-citrulline significantly attenuates PMN-induced cardiac contractile dysfunction in the isolated perfused rat heart subjected to ischemia/reperfusion via a non-NO-mediated mechanism. Â© 2000 Prous Science.
Methods and findings in experimental and clinical pharmacology
Ikeda, Yasuhiko; Young, Lindon; Scalia, Rosario; and Lefer, Allen M., "Cardioprotective effects of citrulline in ischemia/reperfusion injury via a non-nitric oxide-mediated mechanism" (2000). PCOM Scholarly Papers. 457.