Mechanisms of acetylcholine-induced relaxation in dog external and internal ophthalmic arteries.
Mechanisms underlying the relaxant response to acetylcholine (ACh) were examined in dog external (EOA) and internal ophthalmic arteries (IOA). Acetylcholine produced relaxation in EOA and IOA, partially contracted with prostaglandin (PG) F2 alpha. The relaxations induced by ACh in these arteries were not inhibited by endothelium denudation. The ACh (10(-8)-10(-5) M)-induced relaxations in EOA and IOA were abolished by treatment with atropine or indomethacin and markedly suppressed by tranylcypromine, a PGI2 synthesis inhibitor, but not influenced by hexamethonium. On the other hand, the relaxant response to the highest concentration used (10(-4) M) was partially attenuated but not abolished by treatment with atropine, indomethacin or hexamethonium. This relaxation under treatment with atropine was abolished by NG-nitro-L-arginine (L-NA), a nitric oxide synthase inhibitor, but not by indomethacin, whereas the response under treatment with hexamethonium was abolished by indomethacin, but not by L-NA. Combined treatment with indomethacin and L-NA or oxyhaemoglobin abolished the ACh (10(-4) M)-induced relaxation, or reversed it to a contraction. It may be concluded that relaxations induced by low concentrations of ACh in dog EOA and IOA are associated possibly with the release of PGI2 through activation of muscarinic receptors located in subendothelial tissues, including smooth muscle, and the relaxant response to the high concentration (10(-4) M) of ACh is mediated mainly by the release of nitric oxide through activation of nicotinic receptors in nitroxidergic nerves.
Wang
Y
Y
Department of Pharmacology, Shiga University of Medical Sciences, Ohtsu, Japan.
Okamura
T
T
Toda
N
N
D000109:Acetylcholine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001285:Atropine / Q000494:pharmacology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D006584:Hexamethonium Compounds / Q000494:pharmacology; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D019335:Nitroarginine; D009880:Ophthalmic Artery / Q000187:drug effects*; D011976:Receptors, Muscarinic / Q000187:drug effects
D006584:Hexamethonium Compounds; D011976:Receptors, Muscarinic; D019335:Nitroarginine; D001285:Atropine; D001120:Arginine; D000109:Acetylcholine; D007213:Indomethacin