Mechanisms of inhibition of nitric oxide production in a murine model of splanchnic artery occlusion shock.
Nitric oxide has been thought to be a major endothelium-derived relaxing factor which is synthesized from L-arginine and can be selectively inhibited by L-NG-monomethyl arginine. On the other hand, another endothelium-derived vasorelaxant, defined as endothelium-derived hyperpolarizing factor, has been reported. We compared their role in regulating the splanchnic vascular tone in splanchnic artery occlusion shock in the rat. Administration of L-NG-monomethyl arginine (100 mg/kg) given 5 min prior to reperfusion of splanchnic arteries which were occluded for 45 min, produced a significant increase in mean arterial blood pressure. However, the indices of the severity of shock status, including survival time, survival rate and increases in hematocrit, plasma cathepsin D and myocardial depressant factor activity following splanchnic artery occlusion shock were not exacerbated by administration of L-NG-monomethyl arginine. Addition of L-NG-monomethyl arginine (1 mg/ml) induced a small but significant increase in basal vascular tone of superior mesenteric artery rings, but it failed to totally block acetylcholine-induced vasorelaxation (48 +/- 4% relaxation). Although there were no significant changes in basal vascular tone after administration of glibenclamide (30 micrograms/ml), acetylcholine-induced vasorelaxation was significantly attenuated (58 +/- 4% relaxation). When L-NG-monomethyl arginine and glibenclamide were added together, acetylcholine-induced vasorelaxation was almost totally abolished (18 +/- 2% relaxation). Our results indicate that rat splanchnic artery endothelial cells may produce both endothelium-derived relaxing and hyperpolarizing factor. Endothelium-derived relaxing factor plays an important role in the regulation of basal vascular tone of the splanchnic circulation, while endothelium-derived hyperpolarizing factor may be important in modulating the mesenteric blood flow following splanchnic artery occlusion shock.
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Department of Physiology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107.
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Lefer
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D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D004730:Endothelium, Vascular / Q000502:physiology; D005905:Glyburide / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008641:Mesenteric Vascular Occlusion / Q000378:metabolism* / Q000503:physiopathology; D009129:Muscle Tonus / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012769:Shock / Q000503:physiopathology*; D014664:Vasodilation / Q000187:drug effects; D019323:omega-N-Methylarginine
D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine; D000109:Acetylcholine; D005905:Glyburide