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

SP/W-5186, A cysteine-containing nitric oxide donor, attenuates postischemic myocardial injury
SP/W-5186, A cysteine-containing nitric oxide donor, attenuates postischemic myocardial injury
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.
0022-3565
527-537
Liu, Gao-Lin
e34b7402-1498-460b-bb77-590721f67e3c
Christopher, Theodore A.
c40e3333-0c1e-4e1b-9365-87ecbbec3c44
Lopez, Bernard L.
5a036013-f58c-493c-9961-09495903abc9
Gao, Feng
b70fc7ee-1c00-4b32-aa1a-272e603a3add
Guo, Yaping
63f1bfc0-d1f6-4427-9359-84ecc118897a
Gao, Erhe
42801b15-d02c-4972-832d-95dd99fa410c
Knuettel, Karlheinz
f9da52fc-c0eb-4c9c-a3e2-4280b948541f
Feelisch, Martin
8c1b9965-8614-4e85-b2c6-458a2e17eafd
Ma, Xin L.
a93586fc-e73f-4c5d-bc20-a54337ea4950
Liu, Gao-Lin
e34b7402-1498-460b-bb77-590721f67e3c
Christopher, Theodore A.
c40e3333-0c1e-4e1b-9365-87ecbbec3c44
Lopez, Bernard L.
5a036013-f58c-493c-9961-09495903abc9
Gao, Feng
b70fc7ee-1c00-4b32-aa1a-272e603a3add
Guo, Yaping
63f1bfc0-d1f6-4427-9359-84ecc118897a
Gao, Erhe
42801b15-d02c-4972-832d-95dd99fa410c
Knuettel, Karlheinz
f9da52fc-c0eb-4c9c-a3e2-4280b948541f
Feelisch, Martin
8c1b9965-8614-4e85-b2c6-458a2e17eafd
Ma, Xin L.
a93586fc-e73f-4c5d-bc20-a54337ea4950

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)

Record type: Article

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.

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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

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Date deposited: 29 Jun 2012 11:41
Last modified: 08 Nov 2022 02:42

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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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