ENDOTHELIUM-DEPENDENT RELAXATION RESISTANT TO N-G-NITRO-L-ARGININE INRAT AORTA

Experiments were designed to determine whether cyclic GMP-independent relaxation is involved in the endothelium-dependent vascular relaxatio n response of rat aortic strip to acetylcholine. The relaxation respon se to acetylcholine in the presence of 3 x 10(-4) M N-G-nitro-L-argini ne was apparent when the precontraction was induced by norepinephrine at 5 X 10(-9) M or 10(-8) M. The relaxation response to acetylcholine resistant to N-G-nitro-L-arginine was abolished by 10(-6) M atropine, 10 mM tetraethylammonium, or endothelium removal, but was not inhibite d by 10(-5) M indomethacin, 3 x 10(-6) M oxyhemoglobin or 10(-5) M gli benclamide. The response was virtually abolished when the vascular str ips had been preconstricted with 20 mM KCl. The increase in vascular c yclic GMP levels induced by 10(-5) M acetylcholine was completely abol ished by 3 x 10(-4) M N-G-nitro-L-arginine. These results suggest that acetylcholine-induced endothelium-dependent relaxation resistant to N -G-nitro-L-arginine in rat aorta is unmasked when the precontractile f orce is caused by lower concentrations of norepinephrine and the relax ation is mediated by a cyclic GMP-independent mechanism, possibly an e ndothelium-derived hyperpolarizing factor.