Role of catestatin in 2K1C-induced renal hypertension in rats and the underlying mechanism

doi:10.13459/j.cnki.cjap.2016.03.006

Abstract

Abstract: Objective:To investigate the roles of catestatin (CST) in 2-kidney-1 clip (2K1C)-induced renal hypertension in rats, and to explore the underlying mechanism. Methods:Thirty six male SD rats were randomly divided into Sham group (n=15) and Model group(n=21).The model group was performed by 2K1C operation. For 2K1C operation, the left renal arteries were narrowed by cotton thread. The Sham group was treated with the same condition as the 2K1C group except the renal artery was narrowed. Tail-cuff systemic blood pressure of rats was measured before and every weeks after 2K1C operation. Six weeks after 2K1C operation, a carotid artery catheter was inserted to measure blood pressure of rats under anesthesia. Then, the model group was randomly subdivided into 2K1C group (n=15) and 2K1C+CST group (n=6). The rats of 2K1C+CST group were intravenous given CST (80 μg/100 g) and the rats of Sham or 2K1C group were given normal saline. All rats were sacrificed after blood pressure was measured and blood was collected. Then, the left ventricular plus interventricular septum weight (LV+S) was weighted and the ratio of (LV+S)/body weight(BW) was calculated as the index of left ventricular hypertrophy. Norepinephrine (NE) contents in plasma were determined by high performance liquid chromatography(HPLC) and CST contents in plasma by ELISA. The nitrite/nitrate contents in the left ventricular tissue and plasma were measured by nitrate reduction method to represent nitric oxide (NO)contents.Expression levels of CST in the left ventricle, kidney, medulla oblongata and adrenal gland,as well as eNOS and iNOS, were tested by Western blot. Results:①The 2K1C group had higher tail-artery blood pressure(P<0.01) and were more marked presence of right ventricular hypertrophy than those of sham group (P<0.01). Compared with Sham group, plasma CST content in 2K1C group was decreased by 226% (P<0.01), while plasma NE content in 2K1C group was increased by 246% (P<0.01), expression levels of chromograminA(Chga) in medulla oblongata of 2K1C group were increased by 108%, in leftventricle and kidneywere decreased by 60% and 30%, respectively (P<0.05).the content of NO in left ventricular and plasmawere increased by 46% and 24% respectively. ②The carotid arterial blood pressure of 2K1C group markedly reduced after administration of CST.③Compared with 2K1C group, the content of NO in left ventricul and plasma of 2K1C+CST group were increased by 35% and 19% respectively(P<0.05). The expression of eNOS in left ventricular of 2K1C+CST group were also obviously increased. Conclusion:The CST expression of 2K1C-induced renal hypertension rats is reduced and the effects of exogenous CST lowering their blood pressure may be related to NO/NOS system.Therefore, we speculate CST could contribute to the pathogenesis and progression of renal hypertension.

Key words: hypertension, renal, catestatin, nitric oxide, norepinephrine

DING Lu, ZHENG Qing-qing, LI Yang, CHEN Xuan-ying, CHEN Ran, WANG Xue-rui, GONG Yong-sheng, FAN Xiao-fang. Role of catestatin in 2K1C-induced renal hypertension in rats and the underlying mechanism[J]. CJAP, 2016, 32(3): 214-218.

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