Effect of Ovariectomy on Brain Angiotensin Type 1 Receptor Binding, blood pressure, and Hippocampal Gene Methylation and BDNF mRNA expression in Dahl Salt-Sensitive Hypertensive and Dahl Salt-Resistant normotensive Rats

Abstract

Objective: To assess the importance of gonadal steroids for blood pressure regulation, brain AT1 receptors, and regulation of gene expression in the hippocampus of a hypertensive and normotensive rat strain. Background: Women’s resistance to hypertension and cardiovascular disease prior to, but not after menopause, arises from ovarian hormones. Post-menopausally, women are more susceptible to cognitive impairment and dementias. The brain angiotensin system plays a role in cognitive function in addition to regulating the cardiovascular system. Methods: AT1R binding was determined autoradiographically in selected brain regions of ovariectomized versus sham-operated (at 13-weeks) Dahl salt-sensitive (DS) and Dahl salt-resistant (DR) rats which were sacrificed at 33-weeks. Hippocampal DNA methylation was assessed by ELISA, while BDNF mRNA expression was determined by PCR. Mean arterial blood pressure (MAP) was determined telemetrically (DSI technology) at 29-weeks. Results: The MAP of DS sham rats was 181±5mmHg while the MAP of DR sham rats was 96±4mmHg (p1R expression in the solitary tract nucleus of the DS-OVX rats was significantly reduced (p Conclusion: Strain differences and gonadal functionality have limited effects on brain AT1R expression. The global DNA methylation and BDNF mRNA changes suggest gonadal hormone and strain-specific alterations in gene expression in the hippocampus. Grants Funding: NIH NHLBI HL121456, HPD Research Grant, Cardiovascular Neuroscience Fun