Neuropeptide Y-mediated sex- and afferent-specific neurotransmissions contribute to sexual dimorphism of baroreflex afferent function
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Yang Liu1,*, Di Wu2,*, Mei-Yu Qu2,*, Jian-Li He2, Mei Yuan1, Miao Zhao2, Jian-Xin Wang2, Jian He2, Lu-Qi Wang2, Xin-Jing Guo1, Meng Zuo1, Shu-Yang Zhao2, Mei-Na Ma2, Jun-Nan Li1, Weinian Shou3, Guo-Fen Qiao1,2, Bai-Yan Li1
1Department of Pharmacology, Harbin Medical University, Harbin, China
2Key Laboratory of Cardiovascular Research of Ministry of Education, Harbin Medical University, Harbin, China
3Riley 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
Bai-Yan Li, email: firstname.lastname@example.org
Guo-Fen Qiao, email: email@example.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
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 Y1R, not Y2R protein expression, however, both were upregulated upon ovariectomy and canceled by estrogen replacement. Immunostaining confirmed Y1R and Y2R expression in myelinated and unmyelinated afferents. Single-cell PCR demonstrated that Y1R expression/distribution was identical between A- and C-types, whereas, expressed level of Y2R was ~15 and ~7 folds higher in Ah- and C-types than A-types despite similar distribution. Activation of Y1R in nodose elevated BP, while activation of Y2R did the opposite. Activation of Y1R did not alter action potential duration (APD) of A-types, but activation of Y2R- and Y1R/Y2R in Ah- and C-types frequency-dependently prolonged APD. N-type ICa was reduced in A-, Ah- and C-types when either Y1R, Y2R, or both were activated. The sex-difference in Y1R 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.
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