| Background:Renin-angiotensin-aldosterone system(RAAS) and sympathetic nervous system may play important roles in heart failure,Activated microglia in the paraventricular nucleus (PVN) of the hypothalamus may contribute to the release of proinflammatory cytokines(PIC) that stimulate sympathetic nervous systems.In this study,we determined whether blockade of RAAS attenuates PIC and sympathetic drive in heart failure(HF) rats.Methods:Adult male Sprague-Dawley rats(275-300) g underwent left anterior descending coronary artery ligation to induce HF or sham surgery(SHAM).Subsequently,animals were orally treated with inhibitor of mineralocorticoid receptor(spironolactone,SL,1mg/kg/day),or AT1-R(valsartan,VAL,30mg/kg/day).or angiotensin-converting enzyme inhibitor(captopril. 50mg/kg/day),or blocker of microglial activation(minocycline,MIN,10mg/kg/day),or vehicle (VEH)(drinking water) for 4 weeks.At the end of the treatment,rats were anesthetized for hemodynamic and sympathetic nerve recording,calculating heart/body weight(heart/BW),right ventricle/body weight(RVW/BW) and lung/body weight(lung/BW),and then samples were collected for measurements of IL-1βand IL-6 levels in plasma,heart and hypothalamus,NE levels in plasma by ELISA,and activation of microglia in the PVN by immunofluorescence.Results:HF-Treated rats had less PVN microglia activation(P＜0.05),lower IL-1βand IL-6 in plasma,heart and hypothalamus(P＜0.05),lower NE in plasma(P＜0.05),fewer extent of renal sympathetic discharge(P＜0.05),lower left ventricular end-diastolic pressure(LVEDP), lower maximal rate of rise and decline of ventricular pressure(±dp/dtmax),and lower heart/BW, RVW/BW,lung/BW,than VEH-treated HF rats(P＜0.05).HF induced increases in the activated microglia and IL-1βin the PVN compared with sham operated rats(P＜0.05).Conclusion:These findings suggest that blockade of RAAS may reduce HF-induced microglia activation and proinflammatory cytokines in the paraventricular nucleus of hypothalamus,which contributing to the sympathoexcitation in HF. |
