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

Record type: Article

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.

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Citation

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), pp. 527-537. (PMID:9808677).

More information

Published date: 1 November 1998
Organisations: Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 337885
URI: http://eprints.soton.ac.uk/id/eprint/337885
ISSN: 0022-3565
PURE UUID: e1f7fb5f-dbad-4a71-923b-8c72fb041079
ORCID for Martin Feelisch: ORCID iD orcid.org/0000-0003-2320-1158

Catalogue record

Date deposited: 29 Jun 2012 11:41
Last modified: 18 Jul 2017 06:00

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Contributors

Author: Gao-Lin Liu
Author: Theodore A. Christopher
Author: Bernard L. Lopez
Author: Feng Gao
Author: Yaping Guo
Author: Erhe Gao
Author: Karlheinz Knuettel
Author: Martin Feelisch ORCID iD
Author: Xin L. Ma

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