title: Calcitonin gene-related peptide mediated neurogenic vasorelaxation in the isolated canine lingual artery.
abstract: The nature of neurogenic relaxation was investigated in ring preparations of canine lingual artery. In all experiments, the preparations were previously treated with guanethidine (5 x 10(-6) M) to block neurogenic constrictor responses. In the presence of norepinephrine (10(-5) M) to induce tone, electrical stimulation (10 V, 4 to 16 Hz, for 45 sec) produced relaxation of the rings in an endothelium-independent fashion. The relaxant response in endothelium-denuded rings was not changed by propranolol (10(-5) M), and atropine (10(-5) M) did not affect the relaxation elicited by electrical stimulation in endothelium-intact rings. NG-monomethyl-L-arginine (10(-4) M) or NG-nitro-L-arginine methyl ester (10(-4) M), a nitric oxide (NO) synthase inhibitor, had no effect on the electrical stimulation-induced relaxation of endothelium-denuded rings. Human calcitonin gene-related peptide (CGRP)-(8 - 37) (2 x 10(-8) M), a CGRP1-receptor antagonist, inhibited neurogenic relaxation of endothelium-denuded rings; substance P (10(-6) M) failed to mimic the observed effect of electrical stimulation. The demonstrated effect of electrical stimulation was inhibited by glibenclamide (10(-5) M), but not tetraethylammonium (2 x 10(-4) M); glibenclamide abolished the relaxation in response to exogenous CGRP or the ATP-sensitive K+ channel opener cromakalim (10(-6) M) in endothelium-denuded rings. Moreover, tetrodotoxin (3.13 x 10(-6) M) inhibited the relaxation of endothelium-denuded rings induced by electrical stimulation. The relaxation was selectively inhibited when endogenous CGRP had been depleted from perivascular nerves by capsaicin (10(-6) M). These results suggest that CGRP, but not NO, released from non-adrenergic non-cholinergic nerves by electrical stimulation produces relaxation of canine lingual artery that is mediated by activation of CGRP1 receptors.
authors.affiliation: Department of Pharmacology, Kanagawa Dental College, Japan.
authors.forename: D
authors.initials: D
authors.lastname: Kobayashi
authors.forename: K
authors.initials: K
authors.lastname: Todoki
authors.forename: S
authors.initials: S
authors.lastname: Ozono
authors.forename: E
authors.initials: E
authors.lastname: Okabe
mesh_terms: D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001578:Benzopyrans / Q000494:pharmacology; D015740:Calcitonin Gene-Related Peptide / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*; D002211:Capsaicin / Q000494:pharmacology; D019806:Cromakalim; D004285:Dogs; D004558:Electric Stimulation; D005260:Female; D005905:Glyburide / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000294:innervation; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors; D009638:Norepinephrine / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000502:physiology; D011433:Propranolol / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D013373:Substance P / Q000494:pharmacology; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology; D019323:omega-N-Methylarginine
chemical_list: D001578:Benzopyrans; D010446:Peptide Fragments; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D011758:Pyrroles; D013757:Tetraethylammonium Compounds; D014665:Vasodilator Agents; D019806:Cromakalim; C058636:calcitonin gene-related peptide (8-37); D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D013373:Substance P; D013779:Tetrodotoxin; D019789:Tetraethylammonium; D001120:Arginine; D011433:Propranolol; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin; D005905:Glyburide; D019331:NG-Nitroarginine Methyl Ester; D009638:Norepinephrine