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 ± 33 PMNs/mm2 in untreated hearts to 89 ± 10 and 76 ± 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. © 2000 Prous Science.
Available at: http://works.bepress.com/lindon_young/37/
This article was published in Methods and findings in experimental and clinical pharmacology, Volume 22, Issue 7, Pages 563-571.
The published version is available at https://journals.prous.com/journals/servlet/xmlxsl/pk_journals.xml_summary_pr?p_JournalId=6&p_RefId=802268&p_IsPs=N.Copyright © 2000 Prous.