Hirano S, Agata N, Hara Y, Iguchi H, Shirai M, Tone H, Urakawa N
Central Research Laboratories, Mercian Corp., Fujisawa, Japan.
J Pharm Pharmacol. 1992 Mar;44(3):244-9. doi: 10.1111/j.2042-7158.1992.tb03591.x.
The mechanism of endothelium-dependent relaxation induced by pirarubicin, (2''R)-4'-O-tetrahydropyranyladriamycin, THP, or carbachol was investigated in the rat isolated aorta. The relaxant effect of THP (1.5 x 10(-6)-4.5 x 10(-5) M) or carbachol (10(-8)-10(-4) M) on the aorta with endothelium was decreased by lowering Ca2+ in the medium. The relaxation induced by THP was not inhibited by pretreatment with verapamil (10(-6)-10(-5) M), and that induced by carbachol was only partially inhibited. However, on replacement of all but 20 mM Na+ with either Li+ or choline, the THP- or carbachol-induced relaxation was inhibited. Furthermore, the relaxing effect of THP or carbachol was inhibited by pretreatment with amiloride (10(-4)-3 x 10(-4) M), with ouabain (10(-4)-10(-3) M), or with K(+)-depletion. These results suggest that the THP- or carbachol-induced relaxation depending on endothelium was affected by modifying the calcium ion concentration, and that a Na(+)-Ca2+ exchange process is involved.
在大鼠离体主动脉中研究了吡柔比星、（2''R）-4'-O-四氢吡喃基阿霉素（THP）或卡巴胆碱诱导的内皮依赖性舒张机制。通过降低培养基中的Ca2+，THP（1.5×10（-6）-4.5×10（-5）M）或卡巴胆碱（10（-8）-10（-4）M）对有内皮的主动脉的舒张作用减弱。THP诱导的舒张不受维拉帕米（10（-6）-10（-5）M）预处理的抑制，卡巴胆碱诱导的舒张仅部分受抑制。然而，用Li+或胆碱替代除20 mM Na+以外的所有离子后，THP或卡巴胆碱诱导的舒张受到抑制。此外，THP或卡巴胆碱的舒张作用受阿米洛利（10（-4）-3×10（-4）M）、哇巴因（10（-4）-10（-3）M）预处理或K+耗竭的抑制。这些结果表明，取决于内皮的THP或卡巴胆碱诱导的舒张受钙离子浓度改变的影响，并且涉及Na（+）-Ca2+交换过程。
