title: Cardiac sympathetic afferent reflex response to intermedin microinjection into paraventricular nucleus is mediated by nitric oxide and γ-amino butyric acid in hypertensive rats.
abstract: Intermedin (IMD) is a member of calcitonin/calcitonin gene-related peptide (CGRP) and involves in the regulation of cardiovascular function in both peripheral tissues and central nervous system (CNS). Paraventricular nucleus (PVN) of hypothalamus is an important site in the control of cardiac sympathetic afferent reflex (CSAR) which participates in sympathetic over-excitation of hypertension. The aim of this study is to investigate whether IMD in the PVN is involved in the inhibition of CSAR and its related mechanism in hypertension. Rats were subjected to two-kidney one-clip (2K1C) surgery to induce renovascular hypertension or sham-operation (Sham). Acute experiments were carried out four weeks later under anesthesia. The CSAR was evaluated with the renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) responses to the epicardial application of capsaicin. The RSNA and MAP were recorded in sinoaortic-denervated, cervical-vagotomized and anesthetized rats. Bilateral PVN microinjection of IMD (25 pmol) caused greater decrease in the CSAR in 2K1C rats than in Sham rats, which was prevented by pretreatment with adrenomedullin (AM) receptor antagonist AM22-52, non-selective nitric oxide (NO) synthase (NOS) inhibitor L-NAME or γ-amino butyric acid (GABA)B receptor blocker CGP-35348. PVN pretreatment with CGRP receptor antagonist CGRP8-37 or GABA(A) receptor blocker gabazine had no significant effect on the CSAR response to IMD. AM22-52, L-NAME and CGP-35348 in the PVN could increase CSAR in Sham and 2K1C rats. These data indicate that IMD in the PVN inhibits CSAR via AM receptor, and both NO and GABA in the PVN involve in the effect of IMD on CSAR in Sham and renovascular hypertensive rats.
authors.affiliation: Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Physiology, Nanjing Medical University, Nanjing 210029, China Laboratory Center for Basic Medical Sciences, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Physiology, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Hai-jian
authors.initials: HJ
authors.lastname: Sun
authors.affiliation: Department of Physiology, Xi'an Medical University, Shanxi 710021, China.
authors.forename: Jin-rui
authors.initials: JR
authors.lastname: Chang
authors.affiliation: Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Physiology, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Ding
authors.affiliation: Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Physiology, Nanjing Medical University, Nanjing 210029, China Laboratory Center for Basic Medical Sciences, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Gao
authors.affiliation: Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing 100191, China.
authors.forename: Chao-shu
authors.initials: CS
authors.lastname: Tang
authors.affiliation: Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Physiology, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Guo-qing
authors.initials: GQ
authors.lastname: Zhu
authors.affiliation: Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Physiology, Nanjing Medical University, Nanjing 210029, China zhouyebo666@njmu.edu.cn.
authors.forename: Ye-bo
authors.initials: YB
authors.lastname: Zhou
mesh_terms: D053607:Adrenomedullin / Q000008:administration & dosage*; D000344:Afferent Pathways / Q000187:drug effects*; D000818:Animals; D008297:Male; D008845:Microinjections / Q000379:methods; D009479:Neuropeptides / Q000008:administration & dosage*; D009569:Nitric Oxide / Q000378:metabolism*; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects*; D017207:Rats, Sprague-Dawley; D012018:Reflex; D013564:Sympathetic Nervous System / Q000187:drug effects*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: C499411:Adm2 protein, rat; D009479:Neuropeptides; D053607:Adrenomedullin; D009569:Nitric Oxide; D005680:gamma-Aminobutyric Acid
keywords: Intermedin; cardiac sympathetic afferent reflex; hypertension; nitric oxide; paraventricular nucleus; γ-amino butyric acid