Neuropeptide Y-mediated sex- and afferent-specific neurotransmissions contribute to sexual dimorphism of baroreflex afferent function

// Yang Liu 1, * , Di Wu 2, * , Mei-Yu Qu 2, * , Jian-Li He 2 , Mei Yuan 1 , Miao Zhao 2 , Jian-Xin Wang 2 , Jian He 2 , Lu-Qi Wang 2 , Xin-Jing Guo 1 , Meng Zuo 1 , Shu-Yang Zhao 2 , Mei-Na Ma 2 , Jun-Nan Li 1 , Weinian Shou 3 , Guo-Fen Qiao 1, 2 , Bai-Yan Li 1 1 Department of Pharmacology, Harbin Medical University, Harbin, China 2 Key Laboratory of Cardiovascular Research of Ministry of Education, Harbin Medical University, Harbin, China 3 Riley Heart Research Center, Division of Pediatric Cardiology, Herman B. Wells Center for Pediatric Research, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN, USA * These authors have contributed equally to this work Correspondence to: Bai-Yan Li, email: liby@ems.hrbmu.edu.cn Guo-Fen Qiao, email: qiaogf88@163.com Keywords: neuropeptide Y, baroreflex, nodose ganglion, nucleus tractus solitarii, whole-cell patch techniques Received: October 27, 2015     Accepted: July 16, 2016     Published: September 07, 2016 ABSTRACT Background: Molecular and cellular mechanisms of neuropeptide-Y (NPY)-mediated gender-difference in blood pressure (BP) regulation are largely unknown. Methods: Baroreceptor sensitivity (BRS) was evaluated by measuring the response of BP to phenylephrine/nitroprusside. Serum NPY concentration was determined using ELISA. The mRNA and protein expression of NPY receptors were assessed in tissue and single-cell by RT-PCR, immunoblot, and immunohistochemistry. NPY was injected into the nodose while arterial pressure was monitored. Electrophysiological recordings were performed on nodose neurons from rats by patch-clamp technique. Results: The BRS was higher in female than male and ovariectomized rats, while serum NPY concentration was similar among groups. The sex-difference was detected in Y 1 R, not Y 2 R protein expression, however, both were upregulated upon ovariectomy and canceled by estrogen replacement. Immunostaining confirmed Y 1 R and Y 2 R expression in myelinated and unmyelinated afferents. Single-cell PCR demonstrated that Y 1 R expression/distribution was identical between A- and C-types, whereas, expressed level of Y 2 R was ~15 and ~7 folds higher in Ah- and C-types than A-types despite similar distribution. Activation of Y 1 R in nodose elevated BP, while activation of Y 2 R did the opposite. Activation of Y 1 R did not alter action potential duration (APD) of A-types, but activation of Y 2 R- and Y 1 R/Y 2 R in Ah- and C-types frequency-dependently prolonged APD. N-type I Ca was reduced in A-, Ah- and C-types when either Y 1 R, Y 2 R, or both were activated. The sex-difference in Y 1 R expression was also observed in NTS. Conclusions: Sex- and afferent-specific expression of Neuropeptide-Y receptors in baroreflex afferent pathway may contribute to sexual-dimorphic neurocontrol of BP regulation.