Wong Pui San, Roberts Richard E, Randall Michael D
Pharmacology Research Group, School of Life Sciences, University of Nottingham Medical School, Queen׳s Medical Centre, Nottingham NG7 2UH, United Kingdom.
Pharmacology Research Group, School of Life Sciences, University of Nottingham Medical School, Queen׳s Medical Centre, Nottingham NG7 2UH, United Kingdom.
Eur J Pharmacol. 2015 Mar 5;750:108-17. doi: 10.1016/j.ejphar.2015.01.022. Epub 2015 Jan 22.
Endothelial and smooth muscle Transient Receptor Potential (TRP) channels contribute to regulation of vascular tone. We have previously reported sex differences in the endothelial function in porcine isolated coronary arteries (PCAs). The present study examined the role of TRP channels in endothelium-dependent and H2O2-induced vasorelaxations in male and female PCAs. Distal PCAs were mounted in a wire myograph and precontracted with U46619. Concentration-response curves to bradykinin, H2O2 and A23187 were constructed in the presence of TRP channel antagonists with or without L-NAME and indomethacin to inhibit NO synthase and cyclooxygenase respectively. 2-APB (TRPC & TRPM antagonist) inhibited the maximum relaxation (Rmax) of the bradykinin-induced vasorelaxation and abolished the EDH-type response in PCAs from both sexes. SKF96365 (TRPC antagonist) inhibited the Rmax of bradykinin-induced vasorelaxation in males, and inhibited Rmax of the EDH-type response in both sexes. Pyr3 (TRPC3 antagonist) inhibited both the NO and EDH components of the bradykinin-induced vasorelaxation in males, but not females. RN1734 (TRPV4 antagonist) reduced the potency of the NO component of the bradykinin-induced vasorelaxation in females only, but inhibited the Rmax of the EDH-type component in both sexes. 2-APB, SKF96365 and RN1734 all reduced the H2O2-induced vasorelaxation, whereas Pyr3 had no effect. No differences in expression level of TRPC3 and TRPV4 between sexes were detected using Western blot. Present study demonstrated a clear sex differences in the role TRP channels where TRPC3 play a role in the NO- and EDH-type response in males and TRPV4 play a role in the NO-mediated response in females.
内皮细胞和平滑肌瞬时受体电位（TRP）通道有助于调节血管张力。我们之前报道过猪离体冠状动脉（PCA）内皮功能存在性别差异。本研究检测了TRP通道在雄性和雌性PCA中内皮依赖性及过氧化氢（H2O2）诱导的血管舒张中的作用。将远端PCA安装在血管张力测定仪上，并用U46619进行预收缩。在分别存在TRP通道拮抗剂以及有或无L - NAME和吲哚美辛（分别抑制一氧化氮合酶和环氧化酶）的情况下，构建对缓激肽、H2O2和A23187的浓度 - 反应曲线。2 - 氨基乙氧基二苯硼酸（2 - APB，TRPC和TRPM拮抗剂）抑制了缓激肽诱导的血管舒张的最大舒张幅度（Rmax），并消除了两性PCA中的内皮超极化依赖性（EDH）型反应。SKF96365（TRPC拮抗剂）抑制了雄性缓激肽诱导的血管舒张的Rmax，并抑制了两性中EDH型反应的Rmax。Pyr3（TRPC3拮抗剂）抑制了雄性缓激肽诱导的血管舒张中的一氧化氮（NO）和EDH成分，但对雌性无效。RN1734（TRPV4拮抗剂）仅降低了雌性缓激肽诱导的血管舒张中NO成分的效能，但抑制了两性中EDH型成分的Rmax。2 - APB、SKF96365和RN1734均降低了H2O2诱导的血管舒张，而Pyr3无作用。使用蛋白质免疫印迹法未检测到两性之间TRPC3和TRPV4表达水平的差异。本研究表明TRP通道的作用存在明显的性别差异，其中TRPC3在雄性的NO和EDH型反应中起作用，而TRPV4在雌性的NO介导反应中起作用。
