Insulin increases sympathetic nerve activity in part by suppression of tonic inhibitory neuropeptide Y inputs into the paraventricular nucleus in female rats.
Following binding to receptors in the arcuate nucleus (ArcN), insulin increases sympathetic nerve activity (SNA) and baroreflex control of SNA via a pathway that includes the paraventricular nucleus of the hypothalamus (PVN). Previous studies in males indicate that the sympathoexcitatory response is mediated by α-melanocyte stimulating hormone (α-MSH), which binds to PVN melanocortin type 3/4 receptors (MC3/4R). The present study was conducted in α-chloralose-anesthetized female rats to test the hypothesis that suppression of inhibitory neuropeptide Y (NPY) inputs to the PVN is also involved. In support of this, blockade of PVN NPY Y1 receptors with BIBO 3304 (NPY1x), ArcN insulin nanoinjections, and PVN NPY1x followed by ArcN insulin each increased lumbar SNA (LSNA) and its baroreflex regulation similarly. Moreover, prior PVN injections of NPY blocked the sympathoexcitatory effects of ArcN insulin. Finally, PVN nanoinjections of the MC3/4R inhibitor SHU9119 prevented both the acute (15 min) and longer, more slowly developing (60 min), increases in LSNA in response to ArcN insulin. In conclusion, in females, ArcN insulin increases LSNA, in part, by suppressing tonic PVN NPY inhibition, which unmasks excitatory α-MSH drive of LSNA. Moreover, the steadily increasing rise in LSNA induced by ArcN insulin is also dependent on PVN MC3/4R.
Department of Physiology and Pharmacology, Oregon Health & Science University, Portland, Oregon.
Priscila A
PA
Cassaglia
Department of Physiology and Pharmacology, Oregon Health & Science University, Portland, Oregon.
Zhigang
0000-0002-5828-1904
Z
Shi
Department of Physiology and Pharmacology, Oregon Health & Science University, Portland, Oregon brooksv@ohsu.edu.
Virginia L
VL
Brooks
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D017704:Baroreflex / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D007328:Insulin / Q000008:administration & dosage / Q000494:pharmacology*; D009074:Melanocyte-Stimulating Hormones / Q000494:pharmacology; D008845:Microinjections; D009478:Neuropeptide Y / Q000037:antagonists & inhibitors*; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044104:Receptor, Melanocortin, Type 3 / Q000037:antagonists & inhibitors; D044105:Receptor, Melanocortin, Type 4 / Q000037:antagonists & inhibitors; D017476:Receptors, Neuropeptide Y / Q000037:antagonists & inhibitors; D013564:Sympathetic Nervous System / Q000187:drug effects*
D007004:Hypoglycemic Agents; D007328:Insulin; D009478:Neuropeptide Y; D044104:Receptor, Melanocortin, Type 3; D044105:Receptor, Melanocortin, Type 4; D017476:Receptors, Neuropeptide Y; C514973:melanocortin 3 receptor, rat; C000613745:melanocortin receptor type 4, rat; C097212:neuropeptide Y-Y1 receptor; C103272:SHU 9119; D009074:Melanocyte-Stimulating Hormones; D001120:Arginine; C117416:BIBO 3304
NPY; PVN; SNA; arcuate nucleus; α-MSH