Enhanced expression of Cx43 and gap junction communication in vascular smooth muscle cells of spontaneously hypertensive rats

Wang,Li‑Jie; Liu,Wei‑Dong; Zhang,Liang; Ma,Ke‑Tao; Zhao,Lei; Shi,Wen‑Yan; Zhang,Wen‑Wen; Wang,Ying‑Zi; Li,Li; Si,Jun‑Qiang

doi:10.3892/mmr.2016.5783

Enhanced expression of Cx43 and gap junction communication in vascular smooth muscle cells of spontaneously hypertensive rats

Authors:
- Li‑Jie Wang
- Wei‑Dong Liu
- Liang Zhang
- Ke‑Tao Ma
- Lei Zhao
- Wen‑Yan Shi
- Wen‑Wen Zhang
- Ying‑Zi Wang
- Li Li
- Jun‑Qiang Si
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Affiliations: Department of Physiology, Medical College of Shihezi University, Shihezi, Xinjiang 832002, P.R. China, Department of Gastroenterology, The People's Hospital of Xinjiang Uyghur Autonomous Region, Urumqi, Xinjiang 830001, P.R. China, The Key Laboratory of Xinjiang Endemic and Ethnic Diseases, Medical College of Shihezi University, Shihezi, Xinjiang 832002, P.R. China
Published online on: September 26, 2016 https://doi.org/10.3892/mmr.2016.5783
Pages: 4083-4090
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Niflumic acid (NFA) is a novel gap junction (GJ) inhibitor. The aim of the present study was to investigate the effect of NFA on GJ communication and the expression of connexin (Cx) in vascular smooth muscle cells (VSMCs) of mesenteric arterioles of spontaneously hypertensive rats (SHR). Whole‑cell patch clamp recording demonstrated that NFA at 1x10‑4 M significantly inhibited the inward current and its effect was reversible. The time for charging and discharging of cell membrane capacitance (Cinput) reduced from 9.73 to 0.48 ms (P<0.05; n=6). Pressure myograph measurement showed that NFA at 3x10‑4 M fully neutralized the contraction caused by phenylephrine. The relaxation responses of normotensive control Wistar Kyoto (WKY) rats were significantly higher, compared with those of the SHRs (P<0.05; n=6). Western blot and reverse transcription‑quantitative polymerase chain reaction analyses showed that the mRNA and protein expression levels of Cx43 of the third‑level branch of mesenteric arterioles of the SHRs and WKY rats were higher, compared with those of the first‑level branch. The mRNA and protein expression levels of Cx43 of the primary and third‑level branches of the mesenteric arterioles in the SHRs were higher, compared with those in the WKY rats (P<0.05; n=6). The mRNA levels of Cx43 in the mesenteric arterioles were significantly downregulated by NFA in a concentration‑dependent manner (P<0.01; n=6). The protein levels of Cx43 in primary cultured VSMCs isolated from the mesenteric arterioles were also significantly downregulated by NFA in a concentration‑dependent manner (P<0.01; n=6). These results showed that the vasorelaxatory effects of GJ inhibitors were reduced in the SHRs, which was associated with a higher protein expression level of Cx43 in the mesenteric arterioles of the SHRs. NFA also relaxed the mesenteric arterioles by reducing the expression of Cx43, which decreased blood pressure. Therefore, regulation of the expression of GJs may be a therapeutic target for the treatment of hypertension.

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