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SP/W-5186, A cysteine-containing nitric oxide donor, attenuates postischemic myocardial injury.

Abstract
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 micromol/kg) or high-dose (1 micromol/kg) SP/W-5186 was given intravenously as a bolus. Administration of 0.3 micromol/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.
AuthorsG L Liu, T A Christopher, B L Lopez, F Gao, Y Guo, E Gao, K Knuettel, M Feelisch, X L Ma
JournalThe Journal of pharmacology and experimental therapeutics (J Pharmacol Exp Ther) Vol. 287 Issue 2 Pg. 527-37 (Nov 1998) ISSN: 0022-3565 [Print] United States
PMID9808677 (Publication Type: Journal Article)
Chemical References
  • Cardiovascular Agents
  • Dipeptides
  • Nitric Oxide Donors
  • Platelet Aggregation Inhibitors
  • SP 5186
  • Cysteine
Topics
  • Animals
  • Blood Pressure (drug effects)
  • Cardiovascular Agents (chemistry, pharmacology)
  • Cell Adhesion (drug effects)
  • Cysteine (analysis)
  • Dipeptides (chemistry, pharmacology)
  • Heart Rate (drug effects)
  • Lipid Peroxidation (drug effects)
  • Myocardial Reperfusion Injury (prevention & control)
  • Myocardium (metabolism, pathology)
  • Neutrophils (pathology)
  • Nitric Oxide Donors (chemistry, pharmacology)
  • Platelet Aggregation (drug effects)
  • Platelet Aggregation Inhibitors (chemistry, pharmacology)
  • Rabbits

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