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Leptin differentially increases sympathetic nerve activity and its baroreflex regulation in female rats: role of oestrogen
Author(s) -
Shi Zhigang,
Brooks Virginia L.
Publication year - 2015
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2014.284638
Subject(s) - leptin , endocrinology , medicine , baroreflex , sympathetic nervous system , hypothalamus , estrous cycle , autonomic nervous system , heart rate , blood pressure , obesity
Key points Leptin increases sympathetic nerve activity (SNA) in males, which contributes to obesity‐induced hypertension; however, whether leptin is equally effective in females is unknown. We report that leptin does increase SNA and heart rate in female rats; however, for lumbar and renal SNA, this action is only evident in pro‐oestrus and in oestrogen‐treated ovariectomized rats, but not in ovariectomized or dioestrus rats. Leptin increases SNA and heart rate similarly in male and pro‐oestrus female rats; however, leptin increases arterial pressure only in males. Blockade of MC3/4 receptors in the paraventricular nucleus (PVN) with SHU9119 decreases SNA in leptin‐treated pro‐oestrus rats, suggesting that leptin increases SNA in part by increasing α‐melanocyte‐stimulating hormone drive of PVN presympathetic neurons. Our data establish sex differences in leptin's effects to increase SNA and arterial pressure, which emphasizes the need for enhanced recognition and investigation of sex differences in obesity‐induced sympathoexcitation and hypertension.Abstract Obesity and hypertension are commonly associated, and activation of the sympathetic nervous system is considered to be a major contributor, at least in part due to the central actions of leptin. However, while leptin increases sympathetic nerve activity (SNA) in males, whether leptin is equally effective in females is unknown. Here, we show that intracerebroventricular ( i.c.v. ) leptin increases lumbar (LSNA) and renal (RSNA) SNA and baroreflex control of LSNA and RSNA in α‐chloralose anaesthetized female rats, but only during pro‐oestrus. In contrast, i.c.v. leptin increased basal and baroreflex control of splanchnic SNA (SSNA) and heart rate (HR) in rats in both the pro‐oestrus and dioestrus states. The effects of leptin on basal LSNA, RSNA, SSNA and HR were similar in males and pro‐oestrus females; however, i.c.v. leptin increased mean arterial pressure (MAP) only in males. Leptin did not alter LSNA or HR in ovariectomized rats, but its effects were normalized with 4 days of oestrogen treatment. Bilateral nanoinjection of SHU9119 into the paraventricular nucleus of the hypothalamus (PVN), to block α‐melanocyte‐stimulating hormone (α‐MSH) type 3 and 4 receptors, decreased LSNA in leptin‐treated pro‐oestrus but not dioestrus rats. Unlike leptin, i.c.v. insulin infusion increased basal and baroreflex control of LSNA and HR similarly in pro‐oestrus and dioestrus rats; these responses did not differ from those in male rats. We conclude that, in female rats, leptin's stimulatory effects on SNA are differentially enhanced by oestrogen, at least in part via an increase in α‐MSH activity in the PVN. These data further suggest that the actions of leptin and insulin to increase the activity of various sympathetic nerves occur via different neuronal pathways or cellular mechanisms. These results may explain the poor correlation in females of SNA with adiposity, or of MAP with leptin.