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1 Department of Cell Biology and Center for Neuroscience, University of Alberta, Edmonton, AB, Canada
* To whom correspondence should be addressed. E-mail: teresa.krukoff{at}ualberta.ca.
We tested the hypotheses that estrogen replacement in ovariectomized rats attenuates cardiovascular responses to psychological stress and that NO in the brain mediates these effects. Female rats were ovariectomized (OVX); one group received 17
-estradiol (OVX-E) for 11-12 days and the other received vehicle (OVX-V). Seven days after OVX, OVX-E and OVX-V rats were chronically instrumented for arterial pressure measurements and intracerebroventricular (icv) injections. Four to 5 days later, OVX-E and OVX-V rats received icv injections of L-NNA (88 µg/kg), an inhibitor of constitutive nitric oxide (NO) production, or vehicle. Mean arterial pressure (MAP) and heart rate (HR) responses were then measured in conscious rats exposed to 2 cycles of "1-h restraint/1-h rest". We show that MAP responses in restrained OVX-E rats were attenuated both during restraint and during rest. While inhibition of NO production in the brain had no effect on MAP responses to restraint in OVX-V rats, it augmented responses in restrained OVX-E rats, especially during periods of rest, so that MAPs in restrained OVX-E and OVX-V rats were indistinguishable. Finally, NO levels in hypothalami and brainstems were elevated in restrained OVX-E, but not OVX-V rats, compared to their respective unrestrained controls. These results show that estrogen replacement in OVX rats reduces arterial pressure responses to psychological stress and that these effects are mediated, at least in part, by NO.
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