Sex differences in the role of sympathetic nerve activity in the development of hypertension in humans

Abstract

Hypertension is a prevalent condition with clear links to increased mortality and morbidity. The sympathetic nervous system is a key regulator of blood pressure and sex differences in sympathetic blood pressure regulation may contribute to the reduced hypertension prevalence in premenopausal women compared to young men. However, hypertension in premenopausal women exists and the underlying mechanisms are poorly understood. Furthermore, whilst female hypertension risk is greater after the menopause, the mechanisms promoting hypertension in some postmenopausal women but not others remain unclear. This thesis hypothesised that hypertensive women exhibit altered sympathetic regulation versus normotensive controls. Firstly, the transduction of sympathetic nerve activity into blood pressure was measured in hypertensive and normotensive pre- and postmenopausal women (and equivalent male groups), using an established method. Transduction was increased in hypertensive versus normotensive premenopausal, but not postmenopausal women. Additionally, sympathetic transduction was negatively associated with age in hypertensive women. These data indicate a role for increased sympathetic transduction in hypertensive premenopausal but not postmenopausal women. The hypothesised mechanism driving increased sympathetic transduction in hypertensive premenopausal women (poorer beta-adrenergic receptor function versus normotensive controls), was investigated, but data collection was difficult (due to the COVID-19 pandemic), and this question remains unanswered. Additionally, the thesis aimed to determine whether respiratory modulation of sympathetic activity was altered in postmenopausal versus premenopausal women, given that age does not appear to affect respiratory sympathetic modulation in men. The data showed that respiratory sympathetic modulation is reduced in healthy postmenopausal women compared to younger adults, but that hypertension had no additional effect. As such, poorer respiratory modulation may be a mechanism by which ageing is associated with increased sympathetic activity in women. Overall, these data have contributed to the understanding of two aspects of sympathetic blood pressure regulation in women, with important implications for the understanding of hypertension development in women.

Date of Award	27 Sept 2022
Original language	English
Awarding Institution	University of Bristol
Supervisor	Emma C J Hart (Supervisor) & Tom R Gaunt (Supervisor)