Salusin-β in rostral ventrolateral medulla increases sympathetic outflow and blood pressure via superoxide anions in hypertensive rats

Abstract

Rostral ventrolateral medulla (RVLM) plays crucial roles in central cardiovascular regulation. Salusin-β is a multifunctional bioactive peptide and is expressed in the brain and various peripheral tissues. The present study was designed to identify the expression of salusin-β in the RVLM, and to determine its roles and mechanisms in regulating sympathetic outflow and blood pressure in hypertension. Renovascular hypertension was induced with two-kidney, one-clip (2K1C) method in rats. Acute experiments were carried out 4 weeks after the 2K1C or sham operation under urethane and alpha-chloralose anesthesia. Salusin-β level and the number of salusin-β-like immunopositive neurons in the RVLM were greatly increased in 2K1C rats. Microinjection of salusin-β into the RVLM increased renal sympathetic nerve activity, mean arterial pressure and heart rate, whereas antisalusin-β IgG (SIgG) reduced renal sympathetic nerve activity and mean arterial pressure in 2K1C rats, but not in sham-operated rats. The effects of salusin-β were abolished by the RVLM pretreatment with superoxide anion scavenger tempol or polyethylene glycol superoxide dismutase, or NAD(P)H oxidase inhibitor apocynin, but not attenuated by the RVLM microinjection or intravenous injection of dTyr(CH2)5(Me)AVP, an antagonist of V1 receptors of arginine vasopressin. Salusin-β increased NAD(P)H oxidase activity and superoxide anion level in the RVLM, which were prevented by the pretreatment with SIgG. Microinjection of salusin-β or SIgG into the RVLM had no significant effect on the arginine vasopressin level in the RVLM and plasma. Salusin-β in the RVLM increases sympathetic outflow, blood pressure and heart rate via NAD(P)H oxidase-derived superoxide anions in renovascular hypertensive rats.