TY - JOUR
T1 - Cardioprotective effects of citrulline in ischemia/reperfusion injury via a non-nitric oxide-mediated mechanism
AU - Ikeda, Yasuhiko
AU - Young, Lindon
AU - Scalia, Rosario
AU - Lefer, Allen M.
PY - 2000/1/1
Y1 - 2000/1/1
N2 - 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.
AB - 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.
KW - Cardiac contractility
KW - Coronary flow
KW - Neutrophil adherence
KW - Neutrophils
KW - Nitric oxide release
UR - https://digitalcommons.pcom.edu/scholarly_papers/457
M3 - Article
VL - 22
JO - Methods and findings in experimental and clinical pharmacology
JF - Methods and findings in experimental and clinical pharmacology
ER -