Sex steroid hormones as modulators of neurovascular function

心血管系统是身体适应日常生活压力的关键组成部分。事实上，各种各样的刺激都会引起急性和必要的心血管反应，包括说话、唱歌、走路、站立、锻炼等等。在心血管系统中，交感神经系统(“战斗或逃跑”系统)和阻力血管之间的相互作用控制着许多这样的反射反应。然而，关于这些重要的调节机制，尤其是性激素和性激素对这些机制的影响，仍有许多有待了解。虽然现在人们普遍认为心血管控制机制在男性和女性之间往往不同，但我们仍然不太清楚哪些心血管反射在性别之间存在差异(即对站立的反应与对运动的反应的比较)，以及为什么这种控制机制在男性和女性之间会有所不同。后者可能的候选者包括性激素，特别是雌激素和黄体酮。经过几十年的研究，雌激素对血管的影响已经得到很好的证实。然而，关于雌激素对交感神经系统的影响程度，人们知之甚少，更不知道孕酮对交感神经或血管的影响。因此，这项建议的目的是阐明雌激素和孕激素对年轻健康人类的交感神经和血管效应。这些研究将为交感神经系统和血管系统之间发生的复杂相互作用提供新的见解，特别是在女性身上。我们还设计了这些实验，使我们能够区分雌激素和黄体酮的独立作用。将这些方法与我们的反射性心血管调节的综合措施相结合，我们的目标是为雌激素和孕酮在调节交感神经系统的反射激活中的作用以及在外周血管系统中的下游后果提供新的见解。这些研究的结果将加强我们对人体对日常生活中不同压力源的反应的基本理解。

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.