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Exacerbated pressor and sympatho-excitatory effects of central Elabela in spontaneously hypertensive rats.

Elabela (ELA) is a newly discovered peptide that acts as a novel endogenous ligand of angiotensin receptor-like 1 (APJ) receptor. This study was designed to evaluate the effects of ELA-21 in paraventricular nucleus (PVN) on blood pressure and sympathetic nerve activity in spontaneously hypertensive rats (SHR). Experiments were performed in male Wistar-Kyoto rats (WKY) and SHR. ELA expression was up-regulated in PVN of SHR. PVN microinjection of ELA-21 increased renal sympathetic nerve activity (RSNA), mean arterial pressure (MAP), heart rate (HR), plasma norepinephrine (NE) and arginine vasopressin (AVP) levels in SHR. Intravenous injection of ELA-21 significantly decreased MAP and HR in both WKY and SHR, but only induced a slight decrease in RSNA. APJ antagonist F13A in PVN abolished the effects of ELA-21 on RSNA, MAP and HR. Intravenous infusion of both ganglionic blocker hexamethonium and AVP V1a receptor antagonist SR49059 caused significant reduction in the effects of ELA-21 on RSNA, MAP and HR in SHR, while combined administration of hexamethonium and SR49059 abolished the effects of ELA-21. ELA-21 microinjection stimulated Akt and p85α subunit of PI3K phosphorylation in PVN, whereas PI3K inhibitor LY294002 or Akt inhibitor MK-2206 almost abolished the effects of ELA-21 on RSNA, MAP and HR. Chronic PVN infusion of ELA-21 induced sympathetic activation, hypertension and AVP release accompanied with cardiovascular remodeling in normotensive WKY. In conclusion, ELA-21 in PVN induces exacerbated pressor and sympatho-excitatory effects in hypertensive rats via PI3K-Akt pathway.