Neurogenic relaxations caused by nicotine in isolated cat middle cerebral arteries.
In cat middle cerebral arterial strips denuded of the endothelium, nicotine produced a relaxation that was abolished by treatment with hexamethonium. The relaxation was partially inhibited by treatment with NG-nitro-L-arginine (L-NNA), a nitric oxide (NO) synthase inhibitor, and oxyhemoglobin, an NO scavenger. The remaining relaxation in the media containing L-NNA was abolished in the strips made unresponsive to calcitonin gene-related peptide (CGRP) by its repeated application. However, this was not the case when the strips were made tachyphylaxic to vasoactive intestinal polypeptide. The nicotine-induced relaxation was also partially attenuated by pretreatment with capsaicin; the remaining relaxation was abolished by L-NNA but not by its D-enantiomer. The inhibitory effect of L-NNA was reversed by L- but not D-arginine. Histochemical study revealed that injections of ethanol into the vicinity of pterygopalatine ganglion abolished the positive staining for nicotinamide adenine dinucleotide phosphate diaphorase activity and the CGRP immunoreactivity in perivascular nerves innervating the middle cerebral artery of the ipsilateral side. The nicotine-induced relaxation in the middle cerebral artery from the ethanol-injected side was markedly inhibited compared with that from the nontreated side, whereas the relaxations induced by exogenously applied NO and CGRP were unaffected. We conclude that nicotine stimulates nicotinic receptors in nerve terminals and liberates NO or NO-like substance(s) and CGRP as neurotransmitters in cat middle cerebral arteries.
Ayajiki
K
K
Department of Pharmacology, Shiga University of Medical Science, Ohtsu, Japan.
Okamura
T
T
Toda
N
N
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D002415:Cats; D002536:Cerebral Arteries / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005260:Female; D005724:Ganglia / Q000187:drug effects; D005726:Ganglia, Parasympathetic / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009538:Nicotine / Q000494:pharmacology*; D019335:Nitroarginine; D011978:Receptors, Nicotinic / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects*
D011978:Receptors, Nicotinic; D019335:Nitroarginine; D009538:Nicotine; D001120:Arginine