L-arginine causes whereas L-argininosuccinic acid inhibits endothelium-dependent vascular smooth muscle relaxation.

This study examined the actions of L-arginine, a putative precursor of endothelium-derived nitric oxide, and arginine analogs on endothelium-dependent relaxation of isolated rings of bovine pulmonary artery. L-Arginine did not consistently relax arterial rings unless rings were first rendered refractory to endothelium-dependent relaxation by pretreatment with 1 microM A23187 for 45 min. L-Arginine-elicited relaxation was endothelium-dependent, antagonized by oxyhemoglobin or methylene blue, and unaffected by indomethacin. L-Argininosuccinic acid caused endothelium-dependent contractions and irreversible inhibition of endothelium-dependent but not nitroglycerin-elicited relaxation, which was not overcome by addition of L-arginine. Inhibition of endothelium-dependent relaxation by L-NG-monomethyl arginine, however, was reversible and overcome by L-arginine. Therefore, endothelium-dependent relaxants may cause arginine depletion in endothelial cells and endogenous argininosuccinic acid may modulate the biosynthesis of endothelium-derived nitric oxide from arginine.