Vapiprost hydrochloride

Thromboxane A2 (TXA2) participates in many pathophysiological processes of coronary artery disease. However, its mechanism of TXA2‐induced contraction in the coronary artery remains to be clarified. A multi myograph system was used to measure the isometric tension of the mouse coronary arteries and identify the effect and pathway of TXA2 analogues U46619. Confocal laser scanning microscopy was used to measure the intracellular calcium concentration ([Ca2+]i) in mouse coronary artery smooth muscle cells. Results from the experiment had shown that contraction in coronary artery was generated by U46619 in a concentration‐dependent manner, which was completely abolished by a specific TXA2 receptor blocker, GR32191. PI‐PLC inhibitors U73122 and D609 and Rho‐Kinase inhibitor Y‐27632 can block the U46619 elicited coronary artery contraction in a dose‐dependent manner. Then, the vasoconstriction response to U46619 was obviously inhibited by two pan‐PKC inhibitors chelerythrine or Gӧ6983, and a selective PKCδ inhibitor rottlerin, but was not blocked by a selective PKCζ inhibitor PKC‐PS or a selective PKCβ inhibitor hispidin. Meanwhile, the PKC activator PDBu‐induced vasoconstriction was significantly inhibited by 1 μmol/L nifedipine, then mostly inhibited by 100 μmol/L 2‐APB and 10 μmol/L Y27632. We further found that the response to U46619 was inhibited, respectively, by three calcium channel blockers nifedipine, SKF96356 or 2‐APB in a concentration‐dependent manner. Although Store‐operated Ca2+ (SOC) channels generated the increase of [Ca2+]i in mouse coronary artery smooth muscle cells, SOC channels did not contribute to the vasoconstriction in mouse coronary arteries. Caffeine‐induced sarcoplasmic reticulum (SR) Ca2+ release could obviously induce coronal vasoconstriction. In addition, NPPB, a cell membrane Ca2+ activated C1− channel blocker, could obviously inhibit the U46619‐induced vasoconstriction. The U46619‐induced mouse coronary artery contraction was involved in the increase in [Ca2+]i mediated by Cav1.2, TRPC channels and SR release through the activation of G‐protein‐coupled TP receptors and the kinases signalling pathway in TP downstream proteins, while SOC channels did not participate in the vasoconstriction.