PT  - JOURNAL ARTICLE
AU  - Qian Zou
AU  - Susan W. S. Leung
AU  - Paul M. Vanhoutte
TI  - Activation of Nicotinic Receptors Can Contribute to Endothelium-Dependent Relaxations to Acetylcholine in the Rat Aorta
AID  - 10.1124/jpet.112.192229
DP  - 2012 Jun 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 756--763
VI  - 341
IP  - 3
4099  - http://jpet.aspetjournals.org/content/341/3/756.short
4100  - http://jpet.aspetjournals.org/content/341/3/756.full
SO  - J Pharmacol Exp Ther2012 Jun 01; 341
AB  - Acetylcholine causes endothelium-dependent relaxations in the rat aorta. Both muscarinic acetylcholine receptors (mAChRs) and nicotinic acetylcholine receptors (nAChRs) are expressed in endothelial cells. It is generally accepted that mAChRs are responsible for the endothelium-dependent relaxations evoked by acetylcholine. The present study was designed to investigate whether nAChRs can also be involved in such responses evoked by the cholinergic transmitter. Rings with or without endothelium of aortae of spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) normotensive rats were suspended in organ chambers for the measurement of isometric tension. In WKY aortae the muscarinic antagonist atropine abolished the relaxations to increasing concentrations of acetylcholine, confirming that mAChRs are responsible mainly for the response under control conditions. In SHR aortae, atropine caused only partial inhibition of the endothelium-dependent relaxations to acetylcholine; the remaining decreases in tension were inhibited by the nicotinic antagonist mecamylamine, which did not significantly affect the response in the absence of atropine in either SHR or WKY preparations. Thus, when mAChRs are inhibited, nAChRs mediate relaxation to the cholinergic transmitter in the SHR but not the WKY aorta. Nicotine, a direct agonist of the nicotinic receptor, induced endothelium-dependent relaxations in both SHR and WKY rats via the activation of α7-nAChRs, but not by mecamylamine-sensitive nicotinic receptors (α3 subtype). The acetylcholine-induced, atropine-insensitive relaxations and those to nicotine both involve the phosphatidylinositol 3-kinase/AKT pathway. The present study demonstrates that the activation of nAChRs can contribute to acetylcholine-induced, endothelium-dependent relaxations in the aortae of hypertensive animals and suggests that these receptors may contribute to the endothelium-dependent regulation of vascular tone.