Apelin-13 and APJ in paraventricular nucleus contribute to hypertension via sympathetic activation and vasopressin release in spontaneously hypertensive rats.

Abstract

AIMS:

Apelin is a specific endogenous ligand of orphan G protein-coupled receptor APJ. This study was designed to determine the roles and mechanisms of apelin-13 and APJ in paraventricular nucleus (PVN) in renal sympathetic nerve activity (RSNA), arginine vasopressin (AVP) release and mean arterial pressure (MAP) in spontaneously hypertensive rats (SHR).

METHOD:

Acute experiment was carried out in 13-week-old male SHR and Wistar-Kyoto rats (WKY) under anaesthesia. RSNA and MAP responses to the PVN microinjection were determined. Apelin and APJ expressions were examined with quantitative real-time PCR and Western blot. AVP and noradrenaline were determined with ELISA. Osmotic minipumps were used for chronic PVN infusion in conscious WKY.

RESULTS:

Apelin and APJ in the PVN were up-regulated in SHR. The PVN microinjection of apelin-13 increased, but APJ antagonist F13A decreased the RSNA, MAP, plasma noradrenaline and AVP levels in SHR. N-methyl-D-aspartate receptor (NMDAR) antagonist plus non-NMDAR antagonist abolished the apelin-13-induced sympathetic activation rather than AVP release. NMDAR antagonist or non-NMDAR antagonist alone attenuated the apelin-13-induced sympathetic activation. Chronic infusion of apelin-13 into the PVN in normotensive rats induced hypertension, increased plasma noradrenaline and AVP levels and promoted myocardial atrial natriuretic peptide and beta-myosin heavy chain mRNA expressions, two indicative markers of cardiac hypertrophy.

CONCLUSION:

Apelin-13 and APJ in the PVN contribute to hypertension via sympathetic activation and AVP release in SHR. The sympatho-excitatory effect of apeline-13 is mediated by both NMDAR and non-NMDAR in the PVN. Persistent activation of APJ in the PVN induces hypertension.

• Authors: F Zhang, H-J Sun, X-Q Xiong, Q Chen, Y-H Li, Y-M Kang, J-J Wang, X-Y Gao, G-Q Zhu
• Journal: Acta physiologica (Oxford, England) (Acta Physiol (Oxf)) Vol. 212 Issue 1 Pg. 17-27 (Sep 2014) ISSN: 1748-1716 [Electronic] England
• PMID: 24995933 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

Chemical References

• Apelin Receptors
• Aplnr protein, rat
• Intercellular Signaling Peptides and Proteins
• Receptors, G-Protein-Coupled
• apelin-13 peptide
• Arginine Vasopressin

Topics

• Animals
• Apelin Receptors
• Arginine Vasopressin (metabolism)
• Blotting, Western
• Electrophysiology
• Hypertension (metabolism, physiopathology)
• Intercellular Signaling Peptides and Proteins (metabolism)
• Male
• Paraventricular Hypothalamic Nucleus (metabolism)
• Rats
• Rats, Inbred SHR
• Rats, Inbred WKY
• Receptors, G-Protein-Coupled (metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• Sympathetic Nervous System (physiology)