Differential modulation by estrogen of α2-adrenergic and I1-imidazoline receptor-mediated hypotension in female rats

Abstract

We have recently shown that estrogen negatively modulates the hypotensive effect of clonidine (mixed α2-/I1-receptor agonist) in female rats and implicates the cardiovascular autonomic control in this interaction. The present study investigated whether this effect of estrogen involves interaction with α2- and/or I1-receptors. Changes evoked by a single intraperitoneal injection of rilmenidine (600 μg/kg) or α-methyldopa (100 mg/kg), selective I1- and α2-receptor agonists, respectively, in blood pressure, hemodynamic variability, and locomotor activity were assessed in radiotelemetered sham-operated and ovariectomized (Ovx) Sprague-Dawley female rats with or without 12-wk estrogen replacement. Three time domain indexes of hemodynamic variability were employed: the standard deviation of mean arterial pressure as a measure of blood pressure variability and the standard deviation of beat-to-beat intervals (SDRR) and the root mean square of successive differences in R-wave-to-R-wave intervals as measures of heart rate variability. In sham-operated rats, rilmenidine or α-methyldopa elicited similar hypotension that lasted at least 5 h and was associated with reductions in standard deviation of mean arterial pressure. SDRR was reduced only by α-methyldopa. Ovx significantly enhanced the hypotensive response to α-methyldopa, in contrast to no effect on rilmenidine hypotension. The enhanced α-methyldopa hypotension in Ovx rats was paralleled with further reduction in SDRR and a reduced locomotor activity. Estrogen replacement (17β-estradiol subcutaneous pellet, 14.2 μg/day, 12 wk) of Ovx rats restored the hemodynamic and locomotor effects of α-methyldopa to sham-operated levels. These findings suggest that estrogen downregulates α2- but not I1-receptor-mediated hypotension and highlight a role for the cardiac autonomic control in α-methyldopa-estrogen interaction.