Do stretch sensors expressed by aortic baroreceptors interact with circulating estradiol to mediate baroreflex...

Hypertension, or high blood pressure, is a major risk factor for cardiovascular disease, the leading cause of mortality worldwide. The incidence and the severity of hypertension is higher in middle-aged men than women. The hallmark of hypertension is an increased sympathetic nerve activity to the cardiovascular organs. One mechanism that regulates sympathetic nerve activity is the homeostatic baroreflex which maintains blood pressure at optimal levels for survival. Baroreceptive nerve endings innervating the aortic arch detect stretch at the vascular wall and convey these signals to the hindbrain which subsequently modulates sympathetic nerve activity. Although the baroreflex was described more than 80 years ago, the specific molecular, structural, and functional phenotype of aortic baroreceptors remain to be fully elucidated. Several recent studies suggest the involvement of various ion channels, termed as "Stretch Sensors", in detecting vascular stretch. Stretch sensors are diverse, and they include Piezo, transient receptor potential, acid sensing ion, and epithelial sodium channels. Thus, stretch sensors engaged by aortic baroreceptors may evoke baroreception, leading to the regulation of sympathetic nerve activity and blood pressure. In pathophysiological conditions, impaired engagement of stretch sensors may lead to sympathetic nerve overactivity and sustained elevations in blood pressure. Furthermore, ovarian hormones, particularly estradiol, may interact with stretch sensors, increasing baroreflex sensitivity and leading to cardioprotective effects in women. However, low circulating levels of estradiol, such as in post-menopause, can lead to reduced baroreflex sensitivity, hypertension and cardiovascular disease. In this review, we discuss stretch sensors expressed by aortic baroreceptors, the role they play in baroreception and blood pressure regulation, interplay with estradiol, and the role they play the development of hypertension and mediating sex-specific differences.