Upregulation of brain APJ receptor expression induced by high salt in pressure overload rats / 中国药理学通报

ABSTRACT

Aim To observe the effect of high salt stress on sympathetic nerve activity and brain Apelin and APJ system in pressure overload rats.Methods The suprarenal abdominal aorta was banded in male SD rats to create the pressure overload model.Four weeks later,the rats were fed a high-salt (8%NaCl)diet or a regular-salt (0.3% NaCl)diet for 1 week,and the hemodynamic changes of the rats were recorded.Sym-pathetic activity was evaluated by measuring 24 h uri-nary norepinephrine (NE)by ELISA.Real-time RCR and Western blot method were used to analyze the Ape-lin and APJ expression in the paraventricular nucleus of rats.In another protocol,ML22 1 or benzamil was intracerebroventricularly infused in the aorta banding rats fed with high-salt,and levels of 24 h urinary NE and cardiac index were recorded.In addition,normal SD rats were intracerebroventricularly infused with Na+-rich aCSF for 1 week,and the changes of blood pressure,24 h urine-NE and APJ expression levels were detected.Results In the pressure overload rats fed with high salt diet for 1 week,the mean arterial blood pressure (MAP),heart rate (HR),left ventric-ular end systolic pressure (LVESP),24 h urinary NE and APJ mRNA protein expression in paraventricular nuclear were significantly increased compared with those in control groups (P<0.05 ).However,the he-modynamics,24 h urinary NE and APJ expression showed no significant change in the sham rats fed a high salt diet.In addition,ICV infusion of APJ recep-tor antagonist ML221 or the ENaC antagonist benzamil significantly inhibited the 24 h urinary NE level and HW/BW ratio in the pressure overload rats fed high salt diet (P <0.01 ).Intracerebroventricular infusion of high Na+aCSF for 1 week in normotensive rats also significantly increased the MAP,HR,urinary-NE lev-els and brain APJ expression (P <0.0 1 ).Conclu-sions High salt increases the sympathetic nerve activ-ity in rats with pressure overload model, which is closely related to the brain APJ receptor expression and Na+sensitivity.Brain APJ receptor may be an impor-tant target in the development of salt sensitivity.