| Popis: |
Background and purpose: Previous studies demonstrated that nicotine-induced endothelium-independent vasodilation is mediated by perivascular adrenergic nerves and nerves releasing calcitonin gene-related peptide (CGRPergic nerves). We characterized the nicotinic acetylcholine (ACh) receptor subtype underlying the vasodilation in response to nicotine in rat mesenteric arteries. Experimental approach: Rat mesenteric vascular beds without endothelium were contracted by perfusion with Krebs solution containing methoxamine and the perfusion pressure was measured with a pressure transducer. Key results: Perfusion of nicotine (1–100 μM) for 1 min caused a concentration-dependent decrease in perfusion pressure due to vasodilation. Perfusion of (±)-epibatidine (1–100 nM) (non-selective agonist) or (−)-cytisine (1–100 μM) (partial agonist for nicotinic β2 subtype and full agonist for nicotinic β4 subtype) induced vasodilation in a concentration-dependent manner. Vasodilation induced by nicotine, (−)-cytisine- and (±)-epibatidine was markedly attenuated by guanethidine (5 μM) and pretreatment with capsaicin (1 μM). Mecamylamine (relatively selective antagonist for α3β4 subtype), but not dihydro-β-erythroidine (selective antagonist for α4β2 subtype) or α-bungarotoxin (selective antagonist for α7 subtype), markedly inhibited nicotine-induced vasodilation. Nicotine-induced vasodilation was inhibited by methyllycaconitine at high concentrations (>1 μM), which non-selectively antagonize nicotinic receptors, while a low concentration of 10 nM, which selectively antagonizes α7 subtype, had no effect. (−)-Cytisine and (±)-epibatidine-induced vasodilation were abolished by mecamylamine Conclusion and implications: These results suggest that the nicotinic α3β4 receptor subtype, but not the α7 and α4β2 subtypes, is responsible for the vasodilation in rat mesenteric arteries induced by nicotine- and nicotinic ACh receptor agonists through stimulation of adrenergic and CGRPergic perivascular nerves. British Journal of Pharmacology (2007) 151, 1216–1223. doi:10.1038/sj.bjp.0707331 |
