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Endogenous calcitonin gene-related peptide (CGRP) mediates adrenergic-dependent vasodilation induced by nicotine in mesenteric resistance arteries of the rat.
Br J Pharmacol. 2000 Jul; 130(5):1083-91.BJ

Abstract

1. The mechanisms underlying vasodilator effect of nicotine on mesenteric resistance blood vessels and the role of calcitonin gene-related peptide (CGRP)-containing (CGRPergic) vasodilator nerves were studied in the rat. 2. Mesenteric vascular beds isolated from Wistar rats were perfused with Krebs solution, and perfusion pressure was measured with a pressure transducer. 3. In preparations with intact endothelium and contracted by perfusion with Krebs solution containing methoxamine, perfusion of nicotine (1 - 100 microM) for 1 min caused a concentration-dependent vasodilator response without vasoconstriction. 4. The nicotine-induced vasodilation was markedly inhibited by hexamethonium (nicotinic cholinoceptor antagonist, 10 microM) and blocked by guanethidine (adrenergic neuron blocker, 5 microM). 5. Either denervation by cold storage (4 degrees C for 72 h) or adrenergic denervation by 6-hydroxydopamine (toxin for adrenergic neurons, 2 mM for 20 min incubation, twice) blocked the nicotine-induced vasodilation. 6. Neither endothelium removal with perfusion of sodium deoxycholate (1.80 mg ml(-1), for 30 s) nor treatment with N(omega)-nitro-L-arginine (nitric oxide synthase inhibitor, 100 microM), atropine (muscarinic cholinoceptor antagonist, 10 nM) or propranolol (beta-adrenoceptor antagonist, 100 nM) affected the nicotine-induced vasodilation. 7. In preparations without endothelium, treatment with capsaicin (depleting CGRP-containing sensory nerves, 1 microM) or human CGRP[8 - 37] (CGRP receptor antagonist, 0.5 microM) markedly inhibited the nicotine-induced vasodilation. 8. These results suggest that, in the mesenteric resistanc artery of the rat, nicotine induces vasodilation, which is independent of the function of the endothelium and is involved in activation of CGRPergic nerves. It is also suggested that nicotine stimulates presynaptic nicotinic cholinoceptors on adrenergic nerves to release adrenergic neurotransmitters, which then act on CGRPergic nerves to release endogenous CGRP from the nerve.

Authors+Show Affiliations

Department of Clinical Pharmaceutical Science, Graduate School of Natural Science and Technology, Okayama University, 1-1-1 Tsushimanaka, Okayama 700-8530, Japan. kawasaki@pheasant.pharm. okayama-u.ac.jpNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

10882393

Citation

Shiraki, H, et al. "Endogenous Calcitonin Gene-related Peptide (CGRP) Mediates Adrenergic-dependent Vasodilation Induced By Nicotine in Mesenteric Resistance Arteries of the Rat." British Journal of Pharmacology, vol. 130, no. 5, 2000, pp. 1083-91.
Shiraki H, Kawasaki H, Tezuka S, et al. Endogenous calcitonin gene-related peptide (CGRP) mediates adrenergic-dependent vasodilation induced by nicotine in mesenteric resistance arteries of the rat. Br J Pharmacol. 2000;130(5):1083-91.
Shiraki, H., Kawasaki, H., Tezuka, S., Nakatsuma, A., & Kurosaki, Y. (2000). Endogenous calcitonin gene-related peptide (CGRP) mediates adrenergic-dependent vasodilation induced by nicotine in mesenteric resistance arteries of the rat. British Journal of Pharmacology, 130(5), 1083-91.
Shiraki H, et al. Endogenous Calcitonin Gene-related Peptide (CGRP) Mediates Adrenergic-dependent Vasodilation Induced By Nicotine in Mesenteric Resistance Arteries of the Rat. Br J Pharmacol. 2000;130(5):1083-91. PubMed PMID: 10882393.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Endogenous calcitonin gene-related peptide (CGRP) mediates adrenergic-dependent vasodilation induced by nicotine in mesenteric resistance arteries of the rat. AU - Shiraki,H, AU - Kawasaki,H, AU - Tezuka,S, AU - Nakatsuma,A, AU - Kurosaki,Y, PY - 2000/7/6/pubmed PY - 2000/10/21/medline PY - 2000/7/6/entrez SP - 1083 EP - 91 JF - British journal of pharmacology JO - Br J Pharmacol VL - 130 IS - 5 N2 - 1. The mechanisms underlying vasodilator effect of nicotine on mesenteric resistance blood vessels and the role of calcitonin gene-related peptide (CGRP)-containing (CGRPergic) vasodilator nerves were studied in the rat. 2. Mesenteric vascular beds isolated from Wistar rats were perfused with Krebs solution, and perfusion pressure was measured with a pressure transducer. 3. In preparations with intact endothelium and contracted by perfusion with Krebs solution containing methoxamine, perfusion of nicotine (1 - 100 microM) for 1 min caused a concentration-dependent vasodilator response without vasoconstriction. 4. The nicotine-induced vasodilation was markedly inhibited by hexamethonium (nicotinic cholinoceptor antagonist, 10 microM) and blocked by guanethidine (adrenergic neuron blocker, 5 microM). 5. Either denervation by cold storage (4 degrees C for 72 h) or adrenergic denervation by 6-hydroxydopamine (toxin for adrenergic neurons, 2 mM for 20 min incubation, twice) blocked the nicotine-induced vasodilation. 6. Neither endothelium removal with perfusion of sodium deoxycholate (1.80 mg ml(-1), for 30 s) nor treatment with N(omega)-nitro-L-arginine (nitric oxide synthase inhibitor, 100 microM), atropine (muscarinic cholinoceptor antagonist, 10 nM) or propranolol (beta-adrenoceptor antagonist, 100 nM) affected the nicotine-induced vasodilation. 7. In preparations without endothelium, treatment with capsaicin (depleting CGRP-containing sensory nerves, 1 microM) or human CGRP[8 - 37] (CGRP receptor antagonist, 0.5 microM) markedly inhibited the nicotine-induced vasodilation. 8. These results suggest that, in the mesenteric resistanc artery of the rat, nicotine induces vasodilation, which is independent of the function of the endothelium and is involved in activation of CGRPergic nerves. It is also suggested that nicotine stimulates presynaptic nicotinic cholinoceptors on adrenergic nerves to release adrenergic neurotransmitters, which then act on CGRPergic nerves to release endogenous CGRP from the nerve. SN - 0007-1188 UR - https://www.unboundmedicine.com/medline/citation/10882393/Endogenous_calcitonin_gene_related_peptide__CGRP__mediates_adrenergic_dependent_vasodilation_induced_by_nicotine_in_mesenteric_resistance_arteries_of_the_rat_ L2 - https://doi.org/10.1038/sj.bjp.0703376 DB - PRIME DP - Unbound Medicine ER -