Effects of long-term ovariectomy and estrogen replacement on clonidine-evoked reductions in blood pressure and hemodynamic variability

The present study investigated the influence of 12-week ovariectomy (OVX) and estrogen supplementation (OVXE2) on the acute effects of the centrally acting antihypertensive agent clonidine on blood pressure, hemodynamic variability, and locomotor activity in Sprague-Dawley rats. The effects of estrogen depletion and repletion on the peripherally mediated hypotensive response to hydralazine were also evaluated to determine the selectivity of estrogen-clonidine interaction. The radiotelemetry technique was used for blood pressure and locomotor activity measurements. Three time-domain indices of hemodynamic variability were employed: (1) the standard deviation of mean arterial pressure (SDMAP) as a measure of blood pressure variability, and (2) the standard deviation of R-R intervals (SDRR) and the root mean square of successive differences in R-R intervals (rMSSD) as measures of heart rate variability. In control (sham-operated) rats, clonidine (30 mug/kg, i.p.) elicited significant decreases in MAP, blood pressure variability (SDMAP), and overall heart rate variability (SDRR). The reductions in MAP and its variability index (SDMAP) were significantly augmented in OVX rats and restored to sham-operated levels after estrogen replacement (17beta-estradiol subcutaneous pellet, 14.2 mug/d, 12 weeks). The locomotor activity was reduced by clonidine only in OVX rats. In contrast to clonidine, hydralazine (0.5 mg/kg, i.p.) hypotension was not altered by OVX or estrogen replacement. These findings suggest that estrogen negatively modulates centrally evoked hypotension versus no effect on hypotension of peripheral origin. Further, the results implicate the cardiovascular autonomic control in the enhanced hypotensive response to clonidine in OVX rats.