Beneficial actions of S-nitroso-N-acetylpenicillamine, a nitric oxide donor, in murine traumatic shock.
We studied the effects of the nitric oxide donor, S-nitroso-N-acetylpenicillamine (SNAP), in rat traumatic shock characterized by hypotension, increases in plasma free amino-nitrogen (5.3 +/- 0.5 U/ml vs. 2.5 +/- 0.3 U/ml controls) and intestinal myeloperoxidase activities (2.7 +/- 1.0 U/100 mg vs. 0.2 +/- 0.1 U/100 mg controls), and a survival time of 143 +/- 20 min. Moreover, superior mesenteric artery rings isolated from rats in traumatic shock relaxed to the endothelium-dependent vasodilator acetylcholine only 21 +/- 6% of U-46619 induced contraction. Administration of 100 micrograms/kg SNAP 10 min post-trauma followed by 10 micrograms/kg/h infusion prolonged survival time to 273 +/- 18 min (p < .05), attenuated the increases in plasma free amino-nitrogen (3.1 +/- 0.4 U/ml, p < .05) and tissue myeloperoxidase activities (0.6 +/- 0.3 U/100 mg, p < .05). Moreover, SNAP significantly preserved superior mesenteric artery endothelial function; the vasorelaxation to acetylcholine was 54 +/- 4% (p < .01). Protective effects were not seen in traumatic shock rats treated with the non-NO-donating parent compound N-acetylpenicillamine. These results indicate that SNAP affords significant protection in murine traumatic shock which may be achieved through maintenance of systemic blood pressure, preservation of vascular endothelial integrity, and inhibition of neutrophil-endothelial interaction and the resultant reduced microvascular leakiness.
Christopher
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Department of Physiology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
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Lefer
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D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology; D007082:Ileum / Q000201:enzymology; D066298:In Vitro Techniques; D008297:Male; D017538:Mesenteric Artery, Superior / Q000187:drug effects / Q000503:physiopathology; D009569:Nitric Oxide / Q000378:metabolism*; D009584:Nitrogen / Q000097:blood; D010396:Penicillamine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D026423:S-Nitroso-N-Acetylpenicillamine; D012769:Shock / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D014664:Vasodilation / Q000187:drug effects; D014947:Wounds and Injuries / Q000150:complications
D009569:Nitric Oxide; D026423:S-Nitroso-N-Acetylpenicillamine; D009195:Peroxidase; D010396:Penicillamine; D009584:Nitrogen; D000109:Acetylcholine