NG-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 endothelium-derived relaxing factor(s) other than nitric oxide (NO) in vascular relaxation in response to acetylcholine (ACh) in the rabbit renal artery. ACh (10(-9)-10(-6) M) induced concentration-dependent relaxation of isolated endothelium-intact arterial rings preconstricted with noradrenaline. NG-nitro-L-arginine methyl ester (L-NAME), an inhibitor of NO synthase, partly inhibited the ACh-induced endothelium-dependent relaxation, whereas it almost completely abolished the production of cyclic-3', 5'-guanosine monophosphate (cGMP) in these rings in response to ACh. Methylene blue, an inhibitor of guanylate cyclase, had an essentially similar effect to L-NAME on the relaxation. Indomethacin, an inhibitor of cyclooxygenase, had no effect. High concentrations of potassium chloride (to inhibit endothelium-dependent hyperpolarization), tetraethylammonium (TEA) or 4-aminopyridine (4-AP), a voltage-dependent or Ca(2+)-dependent K+ channel blocker, partly inhibited the relaxation 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 concentration 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-dependent relaxation in the rabbit renal artery is mediated by NO, and by an other factor(s), which relaxes the vascular smooth muscle through opening K+ channels other than ATP-sensitive ones, and/or through the activation of a Na+, K(+)-pump.
Kitagawa
S
S
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Mukogawa Women's University, Nishinomiya, Japan.
Yamaguchi
Y
Y
Kunitomo
M
M
Sameshima
E
E
Fujiwara
M
M
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004351:Drug Resistance; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D008751:Methylene Blue / Q000494:pharmacology; D019335:Nitroarginine; D010042:Ouabain / Q000494:pharmacology; D011817:Rabbits; D014664:Vasodilation / Q000187:drug effects*
D019335:Nitroarginine; D010042:Ouabain; D001120:Arginine; D000109:Acetylcholine; D008751:Methylene Blue