Deleterious effect of salusin-ß in paraventricular nucleus on sympathetic activity and blood pressure via NF-κB signaling in a rat model of obesity hypertension.

ABSTRACT

The paraventricular nucleus (PVN) has been shown to play a critical role in regulating blood pressure and sympathetic activity in obesity hypertension (OH). Salusin-ß is a bioactive peptide with potential roles in mediating cardiovascular activity. The study was designed to test the hypothesis that salusin-ß in the PVN can modulate sympathetic activity and blood pressure in OH. Male Sprague-Dawley rats were used to induce OH by a 12-week feeding of a high-fat diet (42% kcal as fat). Microinjection of salusin-ß into the PVN increased the renal sympathetic nerve activity (RSNA), mean arterial pressure (MAP) and heart rate (HR) in a dose-dependent manner, whereas salusin-ß antibody elicited significant decreases in RSNA, MAP and HR, and abolished the effects of salusin-ß only in the OH rats. As expected, the OH rats had a higher norepinephrine level, which was further increased by salusin-ß. Furthermore, salusin-ß in the PVN accelerated the nuclear translocation of the p65 subunit of nuclear factor kappa B (NF-KB) and the degradation of IKB-α (an endogenous inhibitor of NF-KB). Pretreatment with pyrrolidine dithiocarbamate (an exogenous inhibitor of NF-KB) decreased RSNA, MAP and HR, and abolished the effects of salusin-ß in the PVN in the OH rats. We concluded that salusin-ß in the PVN markedly increased sympathetic outflow and blood pressure in diet-induced OH rats via NF-κB signaling.