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.