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Effects of Ramipril on the expression of connexin 43 in cerebral arteries of spontaneously hypertensive rats

TIAN Tian, TAN Chao-Yang, JIA Qi-Hua, CONG Wen-Wen, TIAN Jun-Jie, MA Ke-Tao, LI Li, SI Jun-Qiang^*

Department of Physiology, Shihezi University Medical College/Xinjiang Key Laboratory of Endemic and Ethnic Diseases, Ministry of Education, Shihezi 832002, China

Abstract

The present study was designed to examine whether Ramipril (an inhibitor of angiotensin-converting enzyme) affected spontaneous hypertension-induced injury of cerebral artery by regulating connexin 43 (Cx43) expression. Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) were randomly divided into WKY, WKY + Ramipril, SHR, and SHR + Ramipril groups (n = 8). The arterial pressure was monitored by the tail-cuff method, and vascular function in basilar arteries was examined by pressure myography. Hematoxylin-eosin (HE) staining was used to show vascular remodeling. The expression and distribution of Cx43 was determined by using immunofluorescence and immunohistochemistry analysis. The protein and mRNA levels of Cx43 were examined by Western blot and real-time PCR analysis, respectively. The results showed that chronic Ramipril treatment significantly attenuated blood pressure elevation (P < 0.01, n = 8) and blood vessel wall thickness in SHR (P < 0.01, n = 8). The cerebral artery contraction rate in the SHR group was higher than that in the WKY group (P < 0.05, n = 8). The cerebral artery contraction rate in the SHR + Ramipril group was lower than that in the SHR group (P < 0.05, n = 8). Pretreatment with 2-APB (Cx43 non-specific blocker) or Gap26 (Cx43 specific blocker) significantly decreased the vasoconstriction rate, while pretreatment with AAP10 (Cx43 non-specific agonist) significantly increased the vasoconstriction in the SHR + Ramipril group (P < 0.05, n = 8). In addition, the expression of Cx43 mRNA and protein in cerebral arteries of SHR group was higher than that of WKY group (P < 0.05, n = 8). The mRNA and protein expression of Cx43 in cerebral arteries of SHR + Ramipril group was significantly lower than that of SHR group (P < 0.05, n = 8). These results suggest that Ramipril can down-regulate the expression of Cx43 mRNA and protein in cerebral arterial cells of SHR, lower blood pressure, promote vasodilation, and improve arterial damage and vascular dysfunction caused by hypertension.

Key words: Ramipril; spontaneous hypertension; rennin-angiotensin-aldosterone system; cerebral artery; connexin 43

Received: 2018-07-03　　Accepted: 2018-09-28

Corresponding author: 司军强　　E-mail: sijunqiang@shzu.edu.cn

DOI: 10.13294/j.aps.2019.0006

Citing This Article：

TIAN Tian, TAN Chao-Yang, JIA Qi-Hua, CONG Wen-Wen, TIAN Jun-Jie, MA Ke-Tao, LI Li, SI Jun-Qiang. Effects of Ramipril on the expression of connexin 43 in cerebral arteries of spontaneously hypertensive rats. Acta Physiol Sin 2019; 71 (3): 395-404 (in Chinese with English abstract).