TY - JOUR 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 SP - 527 LP - 537 VL - 287 IS - 2 AU - Gao-Lin Liu AU - Theodore A. Christopher AU - Bernard L. Lopez AU - Feng Gao AU - Yaping Guo AU - Erhe Gao AU - Karlheinz Knuettel AU - Martin Feelisch AU - Xin L. Ma Y1 - 1998/11/01 UR - http://jpet.aspetjournals.org/content/287/2/527.abstract N2 - 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 ER -