Estradiol alters the chemosensitive cardiac afferent reflex in female rats by augmenting sympathoinhibition and attenuating sympathoexcitation

Abstract

The chemosensitive cardiac vagal and sympathetic afferent reflexes are implicated in driving pathophysiological changes in sympathetic nerve activity (SNA) in cardiovascular disease states. This study investigated the impact of sex and ovarian hormones on the chemosensitive cardiac afferent reflex. Experiments were performed in anaesthetized, sinoaortic baroreceptor denervated male, female and ovariectomized female (OVX) Wistar rats with either intact cardiac innervation or bilateral vagotomy. To investigate the chemosensitive cardiac afferent reflexes renal SNA, heart rate (HR) and arterial pressure (AP) were recorded before and following application of capsaicin onto the epicardial surface of the left ventricle. Compared to males, ovary-intact females displayed similar cardiac afferent reflex mediated changes in renal SNA albeit with a reduced maximum sympathetic reflex driven increase in renal SNA. In females, ovariectomy significantly attenuated the cardiac vagal afferent reflex mediated inhibition of renal SNA (renal SNA decreased 2 ± 17% in OVX versus -50 ± 4% in ovary-intact females, P < 0.05) and augmented cardiac sympathetic afferent reflex mediated sympathoexcitation (renal SNA increased 91 ± 11% in OVX vs 62 ± 9% in ovary-intact females, P < 0.05) so that overall increases in reflex driven sympathoexcitation were significantly enhanced. Chronic estradiol replacement, but not progesterone replacement, begun at time of ovariectomy restored cardiac afferent reflex responses to be similar as ovary-intact females. Vagal denervation eliminated all group differences. The current findings show ovariectomy in female rats, mimicking menopause in women, results in greater chemosensitive cardiac afferent reflex driven sympathoexcitation and does so, at least partly, via the loss of estradiols actions on the cardiac vagal afferent reflex pathway.

Keywords: cardiac afferent; myocardial infarction; sex; sympathetic nerve.