Guanidino succinic acid is not the endogenous source of endothelium-derived relaxing factor in the porcine isolated splenic artery.
The possibility that guanidino succinic acid is the major endogenous source of endothelium-derived relaxing factor has been examined using the porcine isolated splenic artery. Administration of 100 microM NG-nitro-L-arginine methyl ester (L-NAME) caused a substantial, endothelium-dependent contraction of the splenic artery that was inhibited by L-arginine (1 mM) but was unaffected by D-arginine (1 mM). L-NAME enhanced the responsiveness of the splenic artery to 5-hydroxytryptamine in endothelium-intact segments only, and the potentiating action of L-NAME was inhibited by L-arginine but not by D-arginine. Administration of 100 microM guanidino succinic acid did not relax the splenic artery and it did not inhibit or reverse contractions of the splenic artery induced by L-NAME. Administration of guanidino succinic acid, either before or after L-NAME, did not affect the potentiating action of L-NAME on the 5-hydroxytryptamine-induced contraction of the splenic artery in endothelium-intact segments. Although substance P caused an endothelium-dependent relaxation of preconstricted segments of the splenic artery, guanidino succinic acid did not relax preconstricted, endothelium-intact or endothelium-denuded segments of the artery. L-NAME inhibited the relaxation induced by substance P in endothelium-intact preparations. The findings for the effects of arginine are consistent with L-arginine being a source of endothelium-derived relaxing factor in the porcine splenic artery, while observations with guanidino succinic acid indicate that it is not a substrate for the synthesis of endothelium-derived relaxing factor in this blood vessel.
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Department of Physiology and Pharmacology, Faculty of Medicine, Queen's Medical Centre, University of Nottingham, United Kingdom.
D000818:Animals; D005260:Female; D006146:Guanidines / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis*; D013157:Splenic Artery / Q000378:metabolism*; D013386:Succinates / Q000378:metabolism*; D013552:Swine
D006146:Guanidines; D013386:Succinates; D009569:Nitric Oxide; C001318:guanidinosuccinic acid