Mechanisms underlying endothelium-independent relaxation by acetylcholine in canine retinal and cerebral arteries.
Canine retinal central arterial strips responded to acetylcholine with a relaxation that was endothelium-independent. Indomethacin and atropine abolished the relaxation at low doses (10(-7) to 10(-6) M) and moderately attenuated the response to high concentrations (10(-5) and 10(-4) M). The residual relaxation at 10(-5) and 10(-4) M in indomethacin-treated strips were abolished by NG-nitro-L-arginine, hexamethonium, oxyhemoglobin and methylene blue, and the NG-nitro-L-arginine-induced inhibition was reversed by L-arginine. Cerebral arterial strips with endothelium responded to acetylcholine with a transient relaxation followed by a contraction, whereas only a relaxation was induced when endothelium was denuded. The relaxations at low and high doses were modified by atropine, indomethacin, hexamethonium and NG-nitro-L-arginine quite similarly to those seen in retinal arteries. Histochemical study demonstrated the presence of perivascular nerves containing NADPH diaphorase in whole mount preparations of the retinal artery. It is concluded that acetylcholine-induced retinal arterial relaxations, independent of endothelium, are mediated possibly by prostaglandin I2 in activation of muscarinic receptors and by nitric oxide derived from perivascular nerves in response to nicotinic receptor stimulation. On the other hand, vasoconstrictor prostanoids appear to be liberated from the endothelium by muscarinic receptor stimulation in cerebral arteries, and mechanisms underlying the relaxation are similar to those seen in retinal arteries.
Toda
N
N
Department of Pharmacology, Shiga University of Medical Sciences, Ohtsu, Japan.
Zhang
J X
JX
Ayajiki
K
K
Okamura
T
T
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D002536:Cerebral Arteries / Q000187:drug effects* / Q000294:innervation / Q000502:physiology; D004285:Dogs; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000294:innervation / Q000502:physiology; D005260:Female; D006651:Histocytochemistry; D066298:In Vitro Techniques; D008297:Male; D018721:Muscarinic Agonists / Q000494:pharmacology; D009126:Muscle Relaxation / Q000187:drug effects; D009252:NADPH Dehydrogenase / Q000378:metabolism; D009412:Nerve Fibers / Q000201:enzymology; D018722:Nicotinic Agonists / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000378:metabolism; D012161:Retinal Artery / Q000187:drug effects* / Q000294:innervation / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
D018721:Muscarinic Agonists; D018722:Nicotinic Agonists; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D019001:Nitric Oxide Synthase; D009252:NADPH Dehydrogenase; D000109:Acetylcholine