Over-expression of SK2 channel in PVN reduces renal sympathetic nerve activity in chronic heart failure rats / 中国病理生理杂志

ABSTRACT

[ABSTRACT]AIM:Toinvestigatetheeffectofover-expressionofsmall-conductancecalcium-activatedpotassium channel subtype 2 (SK2) in the paraventricular nucleus (PVN) of hypothalamus on heart rate(HR), mean arterial pres-sure (MAP) and renal sympathetic nerve activity (RSNA) of the rats with chronic heart failure (CHF).METHODS:Adenovirus vector encoding SK2 (pDC316-mCMV-EGFP-rKCNN2) was constructed.The CHF model of the male Sprague Dawley ( SD) rats was established by the ligation of anterior descending coronary artery .Echocardiogram was used at the 6th week after the operation to identify the CHF model .Adenovirus vector encoding SK 2 ( pDC316-mCMV-EGFP-rKCNN2) or control adenovirus vector ( pDC316-mCMV-EGFP) were transfected into the PVN in vivo.The cardiac func-tion was monitored by echocardiogram .The expression of SK2 at mRNA and protein levels was determined by RT-PCR, Western blotting and immunofluorescence .The HR, MAP and RSNA were measured by PowerLab 8/30 in anesthetized rats with bilateral PVN microinjection of SK channel blocker apamin .RESULTS:Treatment with pDC316-mCMV-EGFP-rKC-NN2 significantly decreased the renal sympathetic nerve activity in the rat with CHF .Injection of pDC316-mCMV-EGFP did not change the renal sympathetic nerve activity in the rats in sham group .CONCLUSION:The expression and func-tion of SK channels in PVN in the heart failure rats were decreased , suggesting a reduced negative regulation of sympathetic activity in central neural system .Increased expression of SK 2 in the PVN leads to a reduction in sympathetic outflow under the condition of CHF , which may provide a new target for the treatment of heart failure .