Sex steroid hormones as modulators of neurovascular function

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The cardiovascular system is a critical component of the body's adaptations to the stressors of daily life. Indeed, a wide variety of stimuli evoke acute and necessary cardiovascular responses, including talking, singing, walking, standing, exercising, and many more. Within the cardiovascular system, it is interactions between the sympathetic nervous system (the “fight or flight” system) and the resistance blood vessels which govern many of these reflex responses. However, there remains a great deal yet to be understood regarding these important regulatory mechanisms, particularly with respect to the effects of sex and sex hormones on these mechanisms. While it is now widely acknowledged that cardiovascular control mechanisms often differ between men and women, we still possess a poor understanding of which cardiovascular reflexes differ between the sexes (i.e. comparisons of the responses to standing versus the responses to exercising) as well as why such control mechanisms would be different between men and women. Likely candidates for the latter include the sex hormones, particularly estrogen and progesterone. The effects of estrogen on blood vessels has been well established by decades of study. However, much less is known regarding the extent to which estrogen affects the sympathetic nervous system, and even less is known regarding the sympathetic or vascular effects of progesterone. Therefore, the purpose of this proposal is to shed light on the sympathetic and vascular effects of estrogen and progesterone in young healthy humans. These studies will provide novel insight into the complex interactions which occur between the sympathetic nervous system and the vascular system, particularly in women. We have also designed these experiments to allow us to differentiate between the independent effects of estrogen and progesterone. Combining these methodologies with our comprehensive measures of reflex cardiovascular regulation, we aim to provide novel insight into the roles of estrogen and progesterone in governing the reflex activation of the sympathetic nervous system and the downstream consequences in the peripheral vasculature. The results from these studies will enhance our fundamental understanding of the human body's responses to different stressors of daily life in both men and women.