Investigation of the role of nicotinic acetylcholine receptors in the control of vascular tone

Abstract

The endothelium is a thin monolayer of cells that lines the interior surface of all blood vessels and plays several important physiological roles, including in vascular tone modulation via endothelium-dependent relaxation mechanisms. Cholinergic agonists mediate endothelium-dependent relaxation by activating muscarinic acetylcholine receptors (mAChRs) on endothelial cells (ECs). Activating mAChRs releases nitric oxide (NO) and prostacyclin (PGI2 ) and facilitates endothelium-dependent hyperpolarisation (EDH); subsequently, relaxation of adjacent smooth muscle cells (SMCs) occurs. ECs express mAChRs and nicotinic acetylcholine receptors (nAChRs). While it has been established that M 3 mAChRs mediate endothelium-dependent relaxation, the functional roles and activities of nAChRs in regulating vascular tone are still unclear. Alpha 7 nAChRs (α7 nAChRs), which are expressed more widely in non-neuronal cells, have been shown to play an essential role in several physiological and pathophysiological conditions. The present work investigated the role that α7 nAChRs play in resistance arteries, particularly in endothelium-dependent relaxation. Wire (tension) myography was used to study pharmacological responses in rat mesenteric arteries to investigate the relative effects of cholinergic receptors in mediating functional responses to acetylcholine (ACh). Phenylephrine (PE) or U46619 was applied to precontracted arterial segments, which were relaxed using cholinergic agonists in the presence or absence of α7 nAChR antagonists. Nitrite (NO2 - ) and PGI2 were also added to conditioned media to investigate the response of cultured ECs to cholinergic receptor agonists and antagonists. The results show that selective α7 nAChR antagonists enhance ACh-induced endothelium-dependent relaxation in rat mesenteric arteries. In summary, α7 nAChRs act in opposition to mAChRs in response to agonists such as ACh, and these receptors may therefore play a functional role in controlling vascular tone.