RT Journal Article
SR Electronic
T1 SP/W-5186, A Cysteine-Containing Nitric Oxide Donor, Attenuates Postischemic Myocardial Injury
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 527
OP 537
VO 287
IS 2
A1 Gao-Lin Liu
A1 Theodore A. Christopher
A1 Bernard L. Lopez
A1 Feng Gao
A1 Yaping Guo
A1 Erhe Gao
A1 Karlheinz Knuettel
A1 Martin Feelisch
A1 Xin L. Ma
YR 1998
UL http://jpet.aspetjournals.org/content/287/2/527.abstract
AB The effects of SP/W-5186, a cysteine-containing nitric oxide (·NO) donor, on myocardial reperfusion injury were studied in a rabbit ischemia (45 min) and reperfusion (180 min) model. Five min before reperfusion, either low-dose (0.3 μmol/kg) or high-dose (1 μmol/kg) SP/W-5186 was given intravenously as a bolus. Administration of 0.3 μmol/kg SP/W-5186 did not change mean arterial blood pressure, heart rate or pressure-rate index. However, administration of low-dose SP/W-5186 exerted marked cardioprotective effects as evidenced by improved cardiac functional recovery (P < .05 vs.vehicle), decreased plasma creatine kinase concentration (P < .01) and reduced infarct size (P < .01). Moreover, administration of SP/W-5186 significantly decreased platelet aggregation (P < .01 vs. vehicle), attenuated polymorphonuclear leukocyte (PMN) accumulation in myocardial tissue, inhibited PMN adhesion to endothelial cells and preserved endothelial function. Administration of high-dose SP/W-5186 resulted in a transient but significant decrease in mean arterial blood pressure and exerted more cardiac protection compared with low-dose treatment. However, the effects on platelet aggregation, PMN accumulation and PMN adhesion did not differ significantly between the two SP/W-5186 groups. Furthermore, administration of SP/W-6373, an analogue of SP/W-5186 that lacks the NO moiety, failed to exert any protective effects. These results demonstrate that NO released from SP/W-5186 significantly protected myocardial tissue from reperfusion injury. The primary mechanisms of the observed cardioprotection by SP/W-5186 involve inhibition of platelet aggregation, attenuation of PMN-endothelium interaction and preservation of endothelial function. The American Society for Pharmacology and Experimental Therapeutics