Contribution of Baroreflex Afferent Pathway to NPY-Mediated Regulation of Blood Pressure in Rats
Yang Liu 1,2 • Shu-Yang Zhao1 • Yan Feng1 • Jie Sun1 • Xiao-Long Lu3 • Qiu-Xin Yan1 • Ying Li1 • Zhuo Liu 1,4 • Lu-Qi Wang1 • Xun Sun1 • Shijun Li 2 • Guo-Fen Qiao1 • Bai-Yan Li 1
1 Department of Pharmacology, State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Medicine Research, Ministry of Education, College of Pharmacy, Harbin Medical University, Harbin 150081, China
2 Department of Clinical Laboratory, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, China
3 Department of Pharmacology, College of Pharmacy, Dalian Medical University, Dalian 116044, China
4 Riley Heart Center, Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, USA
Neuropeptide Y (NPY), a metabolism-related cardiovascular factor, plays a crucial role in blood pressure (BP) regulation via peripheral and central pathways. The expression of NPY receptors (Y1R/Y2R) specific to baroreflex afferents impacts on the sexually dimorphic neural control of circulation. This study was designed to investigate the expression profiles of NPY receptors in the nodose ganglion (NG) and nucleus tractus solitary (NTS) under hypertensive conditions. To this end, rats with hypertension induced by NG-nitro-L-arginine methylester (L-NAME) or high fructose drinking (HFD), and spontaneously hypertensive rats (SHRs) were used to explore the effects/mechanisms of NPY on BP using functional, molecular, and electrophysiological approaches. The data showed that BP was elevated along with baroreceptor sensitivity dysfunction in model rats; Y1R was up- or down-regulated in the NG or NTS of male and female HFD/L-NAME groups, while Y2R was only down-regulated in the HFD groups as well as in the NG of the male L-NAME group. In SHRs, Y1R and Y2R were both down-regulated in the NTS, and not in the NG. In addition to NPY-mediated energy homeostasis, leptin-melanocortin activation may be essential for metabolic disturbance-related hypertension. We found that leptin and α-melanocyte stimulating hormone (α-MSH) receptors were aberrantly down-regulated in HFD rats. In addition, α-MSH concentrations were reduced and NPY concentrations were elevated in the serum and NTS at 60 and 90 min after acute leptin infusion. Electrophysiological recordings showed that the decay time-constant and area under the curve of excitatory post-synaptic currents were decreased by Y1R activation in A-types, whereas, both were increased by Y2R activation in Ah- or C-types. These results demonstrate that sex- and afferent-specific NPY receptor expression in the baroreflex afferent pathway is likely to be a novel target for the clinical management of metabolism-related and essential hypertension.
Neuropeptide Y; Hypertension; Nucleus of the solitary tract; Excitatory post-synaptic current; Baroreflex