Exploring the Role of the Immune System in Hypertension Development Before and After Menopause

Abstract

The prevalence of hypertension between men and women varies greatly across the lifespan. Prior to menopause, women have lower rates of hypertension compared to age-matched men; while after menopause, the rates of hypertension in women surpass that of male-counterparts. Furthermore, women are known to be less responsive to traditional anti-hypertensive therapeutics and report increased side effects compared to men. Despite these known sexual dimorphisms, no sex-specific therapeutics or clinical guidelines have been developed for women before or after the menopause transition. Sex differences in hypertension are also reported in preclinical models of hypertension. Our group has previously shown that premenopausal females are protected from T-cell mediated Angiotensin (Ang II)-induced hypertension compared to males but following the onset of menopause (using the 4-vinylcyclohexene diepoxide or VCD model), females lose this protection from hypertension. The specific physiologic mechanisms regulating premenopausal protection from immune-mediated hypertension, or how this protection is lost following the onset of menopause are largely unknown. The studies outlined in this thesis aim to address this gap in knowledge and investigate specific changes in the innate and adaptive immune system of pre- and postmenopausal females before or after a hypertensive stimulus. Overall, we demonstrate that menopausal females have an enhanced proinflammatory immune cell environment, particularly in end organs such as the kidney, which likely contributes to the increased susceptibility to hypertension following the onset of menopause.