Effect of BTP2 on agonist-induced vasoconstriction in the mouse aorta in vitro

作者：Zhou, Meng-Yuan; Zhang, Li; Zheng, Dan-Lin; Lai, Ying-Yu; Liu, Pei-Ming; Liu, Lin; Kuang, Su-Juan; Yang, Hui; Rao, Fang; Long, Huang^*; Deng, Chun-Yu^*

来源：Clinical and Experimental Pharmacology and Physiology, 2021, 48(5): 726-734.

DOI：10.1111/1440-1681.13469

• aortic smooth muscle
• BTP2
• phenylephrine
• SOC
• vasoconstriction

BTP2 is a potent inhibitor of store-operated Ca2+ entry (SOCE), which plays a vital role in vasoconstriction. However, the direct effect of BTP2 on the contractile response remains unclear. Here, we investigated the effects and mechanisms of action of BTP2 in the mouse aorta. Isometric tension was measured using a Multi Myograph System with two stainless steel wires. Ca2+ transient was recorded by confocal laser scanning microscope. The results showed that BTP2 markedly suppressed vasoconstriction mediated by SOCE and Ca2+ influx mediated by SOCE. The cumulative concentration of BTP2 had no effect on the baseline of mouse aortic rings, whereas it increased vasoconstriction stimulated by 3 mu mol/L Phenylephrine. BTP2 (1 mu mol/L) significantly increased vasoconstriction induced by 3 mu mol/L Phe or cumulative concentration. BTP2 also promoted noradrenaline-induced aortic contraction. However, Phe- and noradrenaline-induced contraction was not affected by 0.3 or 3 mu mol/L BTP2, and BTP2 at 10 mu mol/L significantly suppressed aortic contraction. BTP2 inhibited 5-HT-evoked contraction in a concentration-dependent manner. BTP2 at higher concentrations (>3 mu mol/L) inhibited CaCl2-induced and 60 mmol/L K+-induced contraction with progressive reduction of maximal contraction in a concentration-dependent manner. These results suggest that 1 mu mol/L BTP2 increases contraction evoked by alpha 1 adrenoreceptor activation. BTP2 at higher concentrations may inhibit Cav1.2 channels.

• 单位
  广东省人民医院; 九江学院; 南方医科大学