Salusin-β in paraventricular nucleus increases blood pressure and sympathetic outflow via vasopressin in hypertensive rats

Salusin-beta is a bioactive peptide with peripheral hypotensive, mitogenic and pro-atherosclerotic effects. The present study was designed to determine the roles of salusin- in the paraventricular nucleus (PVN) and its relationship with arginine vasopressin (AVP) in hypertension and sympathetic activation. Renovascular hypertension was induced by two-kidney, one-clip (2K1C) in male SpragueDawley rats. Acute experiments were carried out 4 weeks after 2K1C or sham-operation under urethane and alpha-chloralose anaesthesia. Renal sympathetic nerve activity (RSNA), mean arterial pressure (MAP), and heart rate (HR) were recorded. Microinjection of salusin- into the PVN increased the RSNA, MAP, and HR in a dose-related manner, whereas anti-salusin- IgG in the PVN decreased the RSNA and MAP, and abolished the effects of salusin- in 2K1C rats. However, either salusin- or anti-salusin- IgG in the PVN failed to cause any significant effects in sham-operated rats. The number of salusin--like immunopositive neurons in the PVN was significantly increased in 2K1C rats. Salusin- in the PVN increased the plasma AVP and norepinephrine levels in 2K1C rats, but not in sham-operated rats. Iv injection of dTyr(CH2)(5)(Me)AVP (an AVP V1-receptor antagonist, AAVP) decreased RSNA and MAP, and abolished the effects of salusin- in the PVN in 2K1C rats. Microinjection of AAVP into the rostral ventrolateral medulla (RVLM), but not into the PVN, abolished the effects of salusin- on RSNA and HR. Salusin- in the PVN increases blood pressure, heart rate, and sympathetic outflow via both circulating AVP and AVP in the RVLM in hypertensive rats.