Neuropeptide Y-mediated sex- and afferent-specific neurotransmissions contribute to sexual dimorphism of baroreflex afferent function.
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.
Department of Pharmacology, Harbin Medical University, Harbin, China.
Yang
Y
Liu
Key Laboratory of Cardiovascular Research of Ministry of Education, Harbin Medical University, Harbin, China.
Di
D
Wu
Key Laboratory of Cardiovascular Research of Ministry of Education, Harbin Medical University, Harbin, China.
Mei-Yu
MY
Qu
Key Laboratory of Cardiovascular Research of Ministry of Education, Harbin Medical University, Harbin, China.
Jian-Li
JL
He
Department of Pharmacology, Harbin Medical University, Harbin, China.
Mei
M
Yuan
Key Laboratory of Cardiovascular Research of Ministry of Education, Harbin Medical University, Harbin, China.
Miao
M
Zhao
Key Laboratory of Cardiovascular Research of Ministry of Education, Harbin Medical University, Harbin, China.
Jian-Xin
JX
Wang
Key Laboratory of Cardiovascular Research of Ministry of Education, Harbin Medical University, Harbin, China.
Jian
J
He
Key Laboratory of Cardiovascular Research of Ministry of Education, Harbin Medical University, Harbin, China.
Lu-Qi
LQ
Wang
Department of Pharmacology, Harbin Medical University, Harbin, China.
Xin-Jing
XJ
Guo
Department of Pharmacology, Harbin Medical University, Harbin, China.
Meng
M
Zuo
Key Laboratory of Cardiovascular Research of Ministry of Education, Harbin Medical University, Harbin, China.
Shu-Yang
SY
Zhao
Key Laboratory of Cardiovascular Research of Ministry of Education, Harbin Medical University, Harbin, China.
Mei-Na
MN
Ma
Department of Pharmacology, Harbin Medical University, Harbin, China.
Jun-Nan
JN
Li
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.
Weinian
W
Shou
Department of Pharmacology, Harbin Medical University, Harbin, China.|Key Laboratory of Cardiovascular Research of Ministry of Education, Harbin Medical University, Harbin, China.
Guo-Fen
GF
Qiao
Department of Pharmacology, Harbin Medical University, Harbin, China.
Bai-Yan
BY
Li
D000200:Action Potentials; D000344:Afferent Pathways / Q000502:physiology*; D000818:Animals; D017704:Baroreflex; D005260:Female; D008297:Male; D009474:Neurons / Q000378:metabolism; D009478:Neuropeptide Y / Q000378:metabolism*; D010052:Ovariectomy; D011311:Pressoreceptors / Q000378:metabolism*; D051381:Rats; D017476:Receptors, Neuropeptide Y / Q000378:metabolism; D012727:Sex Characteristics; D012737:Sex Factors; D009435:Synaptic Transmission / Q000502:physiology*
D009478:Neuropeptide Y; D017476:Receptors, Neuropeptide Y; C097212:neuropeptide Y-Y1 receptor; C095889:neuropeptide Y2 receptor
baroreflex; neuropeptide Y; nodose ganglion; nucleus tractus solitarii; whole-cell patch techniques