Effects of Acute Acetaldehyde, Chronic Ethanol, and Pargyline Treatment on Agonist Responses of the Rat Aorta

Abstract

The purpose of this investigation was to determine the mechanism(s) underlying the vasorelaxant effects of acute versus chronic acetaldehyde (ACA) exposure, in particular, the role of intact endothelium on contractile responses of rat aortic ring segments to potassium chloride (KCl) or norepinephrine (NE). The acute effects of ACA were assessed in preparations from normal animals maintained on a standard rat chow (non-ethanol-ingesting). The monamine oxidase inhibitor, pargyline, elevates plasma ACA levels by decreasing acetaldehyde dehydrogenase activity. Accordingly, preparations from pargyline-treated ethanol-ingesting animals (PE) were used to assess the effects of chronic (12 weeks) ACA and results were compared to those of pargyline-treated non-ethanol-ingesting (P) rats fed a standard liquid diet. In normal and P preparations, maximal inotropic response to KCl and NE were greater in endothelium-denuded than in endothelium-intact preparations. However, in aortic rings obtained from PE rats, the maximal inotropic response to KCl was depressed only in endothelium-denuded rings and that to NE was nearly identical in endothelium-denuded compared to endothelium-intact preparations. Acute ACA (30 mM) exposure significantly reduced both NE- and KCl-induced contractile responses in muscles from all groups. The magnitude of the vasorelaxant effect of this [ACA] on NE-induced responses was endothelium-independent and was similar between groups. However, the vasorelaxant effect of ACA (30 mM) on KCl-induced contractile responses was significantly attenuated in muscles from PE animals with greater inhibition occurring in endothelium-denuded preparations. These results suggest that chronic acetaldehyde exposure leads to an impairment in the inotropic response to membrane depolarization in endothelium-denuded preparations resulting in depressed responsiveness. In addition, the acute vasorelaxant effect of ACA on KCl-induced contractures is significantly attenuated in preparations chronically exposed to ACA which suggests a possible development of tolerance.