Mechanism of contractile dysfunction induced by serotonin in coronary artery in spontaneously hypertensive rats
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ORIGINAL ARTICLE
Mechanism of contractile dysfunction induced by serotonin in coronary artery in spontaneously hypertensive rats Hao Wang 1 & Xiao-Yan Gao 2,3 & Fang Rao 2,3 & Hui Yang 2,3 & Zhao-Yu Wang 2,3 & Lin Liu 2,3 & Su-Juan Kuang 2,3 & Qi Wu 1 & Chun-Yu Deng 2,3 & Jing-Song Xu 1 Received: 17 October 2019 / Accepted: 8 January 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Hypertension is one of the risk factors for coronary heart disease. The present study investigated the mechanism of contractile dysfunction induced by serotonin (5-HT) in coronary artery in spontaneously hypertensive rats (SHRs). Coronary arteries were isolated form SHRs and Wistar rats. Arterial ring contraction was measured using a multi myograph system. Intracellular calcium concentration was measured with a Ca2+ probe fluo-4/AM in vascular smooth muscle cells (VSMCs) isolated from coronary arteries. Signaling pathway–related proteins were assayed by western blotting. A 5-HT2A receptor blocker, sarpogrelate, completely eliminated coronary artery contraction induced by 5-HT. PLCβ inhibitor U73122 also significantly inhibited the response to 5-HT. Compared with the Wistar rats, serotonin (5-HT)– and CaCl2-induced coronary vasoconstriction in the SHRs was significantly reduced. Rho-associated protein kinase inhibitor Y27632, PKC inhibitor rottlerin, and L-type calcium channel blocker nifedipine inhibited the 5-HT-induced coronary artery contraction in a dose-dependent manner in SHRs and Wistar rats. However, the inhibitory effects were reduced in SHRs. In addition, store-operated Ca2+ (SOC) induced an obvious Ca2+ influx in coronary arterial smooth muscle cells, whereas SOC-mediated contraction was very slight in coronary arteries. At the same time, it was found that 5HT2AR, IP3R, and Cav1.2 protein expression and PKCδ activity were decreased, and STIM1 and Orai1 were increased in VSMCs from coronary arteries of SHRs compared with Wistar rats. These results implicate calcium-handling dysfunction mediated by the 5HT2A receptor and downstream signaling pathway might lead to a reduction in 5-HT-induced contraction in SHR coronary arteries. Keywords Hypertension . Spontaneously hypertensive rats . 5-HT . Coronary artery . Vasoconstriction
Introduction Hao Wang and Xiao-Yan Gao contributed equally to this work. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00210-020-01813-5) contains supplementary material, which is available to authorized users. * Chun-Yu Deng [email protected] * Jing-Song Xu [email protected] 1
Department of Cardiology, The Second Affiliated Hospital of Nanchang University, 1 Minde Road, Nanchang 330006, People’s Republic of China
2
Guangdong Provincial Key Laboratory of Clinical Pharmacology, Department of Cardiology, Guangdong Cardiovascular Institute, Guangzhou 510080, China
3
Research Center of Medical Sciences, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, 96 Dongchuan Road, Guangzhou 510080, Peo
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