Alamandine injected into the paraventricular nucleus increases blood pressure and sympathetic activation in spontaneously hypertensive rats

• Published in: Peptides (New York, N.Y. : 1980) N.Y. : 1980), 2018-05, Vol.103, p.98-102
• Main Authors: Shen, Yi-Hui, Chen, Xi-Ru, Yang, Chun-Xi, Liu, Bo-Xun, Li, Peng
• Format: Article
• Language: English
• Subjects: Alamandine; Animals; Blood Pressure - drug effects; cAMP-PKA pathway; Hypertension; Hypertension - metabolism; Hypothalamic paraventricular nucleus; Male; Oligopeptides - pharmacology; Paraventricular Hypothalamic Nucleus - drug effects; Paraventricular Hypothalamic Nucleus - metabolism; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Rats, Sprague-Dawley; Sympathetic activation; Sympathetic Nervous System - drug effects; Sympathetic Nervous System - metabolism
• ISSN: 0196-9781; 1873-5169
• DOI: 10.1016/j.peptides.2018.03.014

•Administration of alamandine in PVN increases blood pressure and sympathetic output.•Alamandine in PVN increases blood pressure and sympathetic output by activating MrgD.•Alamandine exerts more pronounced effects in hypertensive rats than WKY rats.•The cAMP-PKA pathway mediates alamandine’s effects in the PVN. Alamandine is a newly discovered new component of the renin-angiotensin (Ang) system (RAS) that has been shown to exert vasoactive effects in some areas of the nervous system. The present study investigated whether administration of alamandine to the hypothalamic paraventricular nucleus (PVN) modulates blood pressure and sympathetic activity. Mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA) were recorded in anaesthetized rats. PVN microinjection of alamandine increased MAP and RSNA both in Wistar-Kyoto (WKY) rats and in spontaneously hypertensive rats (SHRs), but to a greater extent in SHRs. Moreover, these effects were blocked by pretreatment with alamandine receptor Mas-related G-protein–coupled receptor, member D (MrgD) antagonist D-Pro7-Ang-(1–7), adenylyl cyclase (AC) inhibitor SQ22536, and protein kinase A (PKA) inhibitor rp-adenosine-3′,5′-cyclic monophosphorothionate (Rp-cAMP). Treatment with D-Pro7-Ang-(1–7), SQ22536, or Rp-cAMP alone in PVN decreased MAP and RSNA in the SHRs. Conversely cAMP alone increased MAP and RSNA, and pretreatment with cAMP enhanced alamandine’s effects. These results indicate that microinjection of alamandine into the PVN increases blood pressure and sympathetic outflow via MrgD and the cAMP-PKA pathway.