Previous studies including ours demonstrated a hypotensive response to
ethanol in spontaneously hypertensive rats (SHRs). In this study, we investigated whether this hypotensive effect of
ethanol involves alterations in vascular alpha1-adrenergic receptor responsiveness. The contractile responses to the alpha1-receptor agonist
phenylephrine were evaluated in aortic rings obtained from pair-fed SHRs receiving liquid diet with or without
ethanol (2.5% or 5%, w/v) for 3 months. The responses were measured in aortas with and without endothelium to determine the role of the endothelium in the observed responses. The liquid diet intake was similar in the control and
ethanol groups throughout the study whereas the
body weight was significantly reduced by
ethanol. Cumulative addition of
phenylephrine (1 x 10(-9)-1 x 10(-4) M) caused concentration-related contractile responses. These responses were significantly reduced after endothelium denudation suggesting a role for the endothelium in the modulation of alpha1-receptor responsiveness.
Ethanol (2.5% and 5%) caused significant and concentration-related increases in the contractile responses elicited by
phenylephrine but not KCl. The maximum contraction (Emax) caused by
phenylephrine in rings obtained from SHRs treated with 2.5% and 5%
ethanol amounted to 413.6 +/- 26.3 and 513.0 +/- 46.7 mg tension/mg tissue, respectively, compared with 383.6 +/- 35.2 mg tension/mg tissue in control rings. The enhancement of alpha1 contractions by
ethanol was virtually abolished in rings pretreated with the alpha1-receptor antagonist
prazosin, suggesting upregulation of alpha1-receptors in aortas of
ethanol-fed rats. Endothelium denudation also abolished
ethanol-evoked increases in
phenylephrine contractions. These findings suggest that chronic
ethanol feeding upregulates aortic alpha1-receptors, which may be a consequence of chronic alpha1-receptor blockade by
ethanol. The latter may account, at least in part, for the hypotensive response elicited by
ethanol in SHRs.