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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 5-HT2AR, 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 5-HT2A receptor and downstream signaling pathway might lead to a reduction in 5-HT-induced contraction in SHR coronary arteries.
摘要：
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