SP/W-5186, A cysteine-containing nitric oxide donor, attenuates postischemic myocardial injury
Liu, Gao-Lin, Christopher, Theodore A., Lopez, Bernard L., Gao, Feng, Guo, Yaping, Gao, Erhe, Knuettel, Karlheinz, Feelisch, Martin and Ma, Xin L. (1998) SP/W-5186, A cysteine-containing nitric oxide donor, attenuates postischemic myocardial injury. The Journal of Pharmacology and Experimental Therapeutics, 287, (2), 527-537. (PMID:9808677).
Full text not available from this repository.
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.
|Subjects:||Q Science > QP Physiology
Q Science > QR Microbiology > QR180 Immunology
|Divisions:||Faculty of Medicine > Infection, Inflammation and Immunity
|Date Deposited:||29 Jun 2012 11:41|
|Last Modified:||29 Jun 2012 11:41|
|RDF:||RDF+N-Triples, RDF+N3, RDF+XML, Browse.|
Actions (login required)