Department of Urology, University Hospital, LMU Munich, Munich, Germany.
Pharmacol Res Perspect. 2021 May;9(3):e00771. doi: 10.1002/prp2.771.
Picotamide is a thromboxane A (TXA ) receptor antagonist and TXA synthase inhibitor. In clinical studies, it has been considered as a platelet aggregation inhibitor and improved renal function. In vitro studies suggested inhibition of smooth muscle contraction by picotamide, which is poorly understood. Here, we examined effects of picotamide on contractions of renal interlobar and coronary porcine arteries, induced by different vasoconstrictors. Contractions were induced in an organ bath by agonists or electric field stimulation (EFS). Picotamide inhibited EFS-induced contractions of interlobar arteries around 50% using concentrations of 100 and 300 µM. In interlobar arteries, concentration response curves for contractions induced by three different α -adrenoceptor agonists were shifted to the right by picotamide (2-10-fold increases in EC ). In coronary arteries, α -adrenergic contractions were inhibited without right shift (approx. 50%). Contractions induced by two different cholinergic agonists in coronary arteries were inhibited by picotamide (≥50%) withouth right shift. Inhibition of serotonin-induced contractions by picotamide showed features of a right shift, whereas contractions induced by the TXA analog U46619, angiotensin-II, and endothelin-1 were inhibited by picotamide in interlobar and coronary arteries without right shifts and to different degree. Picotamide inhibits a wide spectrum of vasoconstrictor-induced contractions in porcine interlobar and coronary arteries. Inhibition of vasocontraction may contribute to beneficial effects of picotamide in the cardiovascular system and kidney.
比卡胺是血栓素 A(TXA)受体拮抗剂和 TXA 合酶抑制剂。在临床研究中,它被认为是一种血小板聚集抑制剂,可改善肾功能。体外研究表明,比卡胺抑制平滑肌收缩,但这一机制尚不清楚。在此,我们研究了比卡胺对不同血管收缩剂诱导的肾叶间和冠状动脉猪动脉收缩的影响。在器官浴中,通过激动剂或电刺激(EFS)诱导收缩。100 和 300 μM 浓度的比卡胺可抑制叶间动脉 EFS 诱导的收缩约 50%。在叶间动脉中,比卡胺使三种不同的α-肾上腺素能受体激动剂诱导的收缩浓度反应曲线右移(EC 值增加 2-10 倍)。在冠状动脉中,α-肾上腺素能收缩被比卡胺抑制而无右移(约 50%)。两种不同的胆碱能激动剂诱导的冠状动脉收缩也被比卡胺抑制(≥50%)而无右移。比卡胺抑制 5-羟色胺诱导的收缩具有右移特征,而比卡胺抑制叶间和冠状动脉中 TXA 类似物 U46619、血管紧张素-II 和内皮素-1 诱导的收缩无右移且程度不同。比卡胺抑制猪叶间和冠状动脉中多种血管收缩剂诱导的收缩。血管收缩的抑制可能有助于比卡胺在心血管系统和肾脏中的有益作用。