Expression and Function of Nicotinic Acetylcholine Receptors (nAChR) in Rat and Human Uterine Artery.

Abstract

Introduction: During pregnancy, proper perfusion of uterine arteries is essential for fetal development. Fetal growth retardation by uterine malperfusion can be caused by nicotine. Nicotine activates neuronal nicotinic acetylcholine receptors (nAChR) present in the nervous system and in non-neuronal tissues (e.g. aortal endothelium). nAChR consist of five subunits with homo- and heteropentamers being constructed from eight different ligand binding α- (α2 to α7, α9, α10) and three different β-subunits (β2 to β4). The aim of this study was to quantify changes in diameter of the rat uterine artery lumen following nicotine application and investigate the role of nAChR in nicotine induced luminal changes. Furthermore, distribution of ligand binding α-subunits in the vessel wall of rat and human uterine artery was examined. Methods: In a video-electronic arteriograph system (Living Systems Instrumentation, Burlington, USA) diameters of isolated rat uterine arteries were continously recorded at controlled transmural pressures. Dose-response curves for changes in lumen-diameter due to nicotine were recorded for vessels with and without endothelium in early and late pregnant rats as well as in non-pregnant rats. By means of immunohistochemistry and RT-PCR, distribution of α-subunits in the vessel wall of rat and human uterine artery was analysed. Results: Nicotine caused dose-dependent vasoconstriction that showed a maximum of 30% reduction of vessel-diameter and was reduced up to 75% in endothelium denuded uterine arteries. Dose-response curves of pregnant and non-pregnant rat vessels were nearly identical. Vasoconstriction due to nicotine was reduced by application of specific nAChR subunits blockers indicating involvement of α7- and α4 βsubunits in the nicotinic vasoconstrictive effect. Immunohistochemically, subunits α3, α4, α5, α7, α9 and α10 were localised in endothelium and smooth muscle cells of rat and human uterine artery. Conclusions: Our investigations showed a dose- and endothelium-dependent vasoconstriction of the rat uterine artery following application of nicotine. The effects were not influenced by pregnancy. Through interaction with nAChR α-subunits in endothelium and smooth muscle cells nicotine may directly influence lumen-diameter of the uterine artery resulting in uterine malperfusion.