Activation of n-AChRs contributes to endothelium-dependent relaxations in the rat aorta

Abstract

OBJECTIVE: Muscarinic (mAChRs) and nicotinic (nAChRs) acetylcholine receptors are both expressed in endothelial cells. It is generally accepted that mAChRs are responsible for both endothelium-dependent relaxations and contractions evoked by acetylcholine. The present study was designed to study whether or not nAChRs are also involved in endothelium-dependent relaxations. METHODS: Rat aortic rings with or without endothelium were suspended in organ chambers for isometric tension recording. Quiescent rings were incubated with vehicle, mecamylamine (nAChRs inhibitor),atropine (mAChRs inhibitor,),mecamylamine plus atropine, L-NAME (NO synthase inhibitor) or TRAM-34 plus UCL-1684 (inhibitors of EDHF-mediated responses). All rings were incubated with indomethacin(non-selective cyclooxygenase inhibitor) to prevent endothelium - dependent contractions. After 40 minutes of incubation, they were contracted with phenylephrine and then relaxed with cumulatively increasing concentrations of acetylcholine or nicotine. RESULTS: (1) In both SHR and WKY aortae, cetylcholine-induced relaxations were similar in control and mecamyl-amine -treated rings, while the relaxations were significantly reduced in atropine-treated preparations. In rings of 36 weeks old SHRs, the remaining response in the presence of atropine approximated 50%of those observed in untreated control preparations, and was prevented by mecamylamine. In both 36 weeks and 64 weeks old WKY aortae the remaining response in atropine-treated preparations was minimal. (2) In both SHR and WKY aortae, nicotine induced up to 60% endothelium-dependent relaxation and the relaxations were abolished by L-NAME.TRAM-34 plus UCL-1684 partially inhibited the nicotine-induced relaxations in WKY but not in SHR aorta. CONCLUSION: In the SHR and WKY aorta, mAChRs are mainly responsible for endothelium - dependent relaxations under control conditions. However, when mAChRs are inhibited by atropine, nAChRs mediate relaxations to the cholinergic transmitter in the SHR but not the WKY aorta.