EFFECTS OF ACUTE ACETALDEHYDE, CHRONIC ETHANOL, AND PARGYLINE TREATMENT ON AGONIST RESPONSES OF THE RAT AORTA

The purpose of this investigation was to determine the mechanism(s) un derlying the vasorelaxant effects of acute versus chronic acetaldehyde (ACA) exposure, in particular, the role of intact endothelium on cont ractile responses of rat aortic ring segments to potassium chloride (K CI) or norepinephrine (NE). The acute effects of ACA were assessed in preparations from normal animals maintained on a standard rat chow (no n-ethanol-ingesting). The monamine oxidase inhibitor, pargyline, eleva tes plasma ACA levels by decreasing acetaldehyde dehydrogenase activit y. 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-i ngesting (P) rats fed a standard liquid diet. In normal and P preparat ions, maximal inotropic response to KCI and NE were greater in endothe lium-denuded than in endothelium-intact preparations. However, in aort ic rings obtained from PE rats, the maximal inotropic response to KCI was depressed only in endothelium-denuded rings and that to NE was nea rly identical in endothelium-denuded compared to endothelium-intact pr eparations. Acute ACA (30 mM) exposure significantly reduced both NE- and KCI-induced contractile responses in muscles from all groups. The magnitude of the vasorelaxant effect of this [ACA] on NE-induced respo nses was endothelium-independent and was similar between groups. Howev er, the vasorelaxant effect of ACA (30 mM) on KCI-induced contractile responses was significantly attenuated in muscles from PE animals with greater inhibition occurring in endothelium-denuded preparations. The se results suggest that chronic acetaldehyde exposure leads to an impa irment in the inotropic response to membrane depolarization in endothe lium-denuded preparations resulting in depressed responsiveness. In ad dition, the acute vasorelaxant effect of ACA on KCI-induced contractur es is significantly attenuated in preparations chronically exposed to ACA which suggests a possible development of tolerance. (C) 1996 Acade mic Press, Inc.