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Bosentan ameliorates hypertension in rats exposed to chronic intermittent hypoxia through inhibiting renal sympathetic nerve activity

YANG Sheng-Chang¹, GUO Ya-Jing², YU Fu-Yang¹, CHEN Ling-Ling³, LI Wen-Ya¹, JI En-Sheng^1,*

¹Department of Physiology, Hebei University of Chinese Medicine, Shijiazhuang 050200, China；²Scientific Research Center, Hebei University of Chinese Medicine, Shijiazhuang 050200, China；³Department of Pharmacy, Xixi Hospital of Hangzhou, Hangzhou 310012, China

Abstract

The purpose of this study is to investigate the effect of the oral endothelin antagonist Bosentan on blood pressure and renal sympathetic nerve activity (RSNA) in rats exposed to chronic intermittent hypoxia (CIH), and to explore the sympathoexcitation mechanism of endothelin-1 (ET-1) in CIH-induced hypertension. Twenty-four male SD rats were randomly divided into normoxia, CIH and Bosentan groups. Rats in the normoxia group were exposed to normoxic environment, and rats in CIH or Bosentan group were exposed to intermittent hypoxia for 3 weeks. Bosentan was given at 50 mg/kg by intragastric administration before intermittent hypoxia exposure in Bosentan group. Systolic blood pressure (SBP) was measured by BP-2000, and the change of RSNA to sodium nitroprusside (SNP) or phenylephrine (PE) was recorded by PowerLab signal acquisition system. Serums of all rats were collected and the contents of ET-1 and norepinephrine (NE) were measured by ELISA. Results showed that blood pressure was gradually increased following CIH exposure compared with the normoxia group during the 3 weeks (P < 0.01, P < 0.01, P < 0.001). The basal RSNA was increased and baroreflex sensitivity was decreased in rats exposed to CIH. Furthermore, the blood pressure was positively correlated with the level of ET-1 in serum in rats exposed to CIH (r = 0.833, P = 0.01). Bosentan administration significantly decreased SBP and basal RSNA, increased the baroreflex sensitivity, and decreased serum NE level in rats exposed to CIH. These results suggest that ET-1 is related with blood pressure elevation in rats exposed to CIH, and Bosentan reverses CIH-induced hypertension by decreasing RSNA.

Key words: chronic intermittent hypoxia; endothelin-1; hypertension; renal sympathetic nerve activity

Received: 2018-01-07　　Accepted: 2018-07-11

Corresponding author: 吉恩生　　E-mail: jesphy@126.com

DOI: 10.13294/j.aps.2018.0051

Citing This Article：

YANG Sheng-Chang, GUO Ya-Jing, YU Fu-Yang, CHEN Ling-Ling, LI Wen-Ya, JI En-Sheng. Bosentan ameliorates hypertension in rats exposed to chronic intermittent hypoxia through inhibiting renal sympathetic nerve activity. Acta Physiol Sin 2018; 70 (4): 354-360 (in Chinese with English abstract).