N-G-NITRO-L-ARGININE-RESISTANT ENDOTHELIUM-DEPENDENT RELAXATION INDUCED BY ACETYLCHOLINE IN THE RABBIT RENAL-ARTERY

Studies were designed to determine the extent of the involvement of en dothelium-derived relaxing factor(s) other than nitric oxide (NO) in v ascular relaxation in response to acetylcholine (ACh) in the rabbit re nal artery. ACh (10(-9)-10(-6) M) induced concentration-dependent rela xation of isolated endothelium-intact arterial rings preconstricted wi th noradrenaline. N-G-nitro-L-arginine methyl ester (L-NAME), an inhib itor of NO synthase, partly inhibited the ACh-induced endothelium-depe ndent relaxation, whereas it almost completely abolished the productio n of cyclic-3', 5'-guanosine monophosphate (cGMP) in these rings in re sponse to ACh. Methylene blue, an inhibitor of guanylate cyclase, had an essentially similar effect to L-NAME on the relaxation. Indomethaci n, an inhibitor of cyclooxygenase, had no effect. High concentrations of potassium chloride (to inhibit endothelium-dependent hyperpolarizat ion), tetraethylammonium (TEA) or 4-aminopyridine (4-AP), a voltage-de pendent or Ca2+-dependent K+ channel blocker, partly inhibited the rel axation while, in contrast, glibenclamide, an ATP-sensitive K+ channel blocker, had no effect. Ouabain, an inhibitor of Na+, K+-ATPase, also partly inhibited the ACh-induced relaxation, especially the higher co ncentration effect. Application of L-NAME together with ouabain, TEA, or a high concentration of potassium chloride completely abolished the relaxation. These results suggest that ACh-induced endothelium-depend ent relaxation in the rabbit renal artery is mediated by NO, and by an other factor(s), which relaxes the vascular smooth muscle through ope ning K+ channels other than ATP-sensitive ones, and/or through the act ivation of a Na+, K+-pump.