Department of Medical Pharmacology, Gulhane School of Medicine, Ankara, Turkey.
Int Endod J. 2010 Jul;43(7):590-9. doi: 10.1111/j.1365-2591.2010.01732.x. Epub 2010 May 11.
To test the hypothesis that, Epiphany, either in its mixed form or as separate components, can alter the vascular reactivity of isolated rat thoracic aorta. The possible mechanism of its vascular action was also investigated.
The relaxant effect of the base, the catalyst and mixed Epiphany on isolated rat aortic rings pre-contracted with phenylephrine (PE) was tested. The aortic rings were then incubated with either nitric oxide synthase (NOS) inhibitor, cyclooxygenase (COX) inhibitor or K(+) channel inhibitors; after pre-contraction with PE, relaxations to the various compounds of Epiphany were examined. In another set of experiments, to investigate the Ca(2+)channel antagonistic effect of the Epiphany, the effect of these compounds in Ca(2+)-free solution on extracellular Ca(2+)(CaCl(2))-induced contraction in high-K(+) pre-challenged rings (in K(+)-depolarized rings) was examined to determine whether the direct inhibition of [Ca(2+)] influx increase accounted for the vasodilatory effects of these compounds. For comparison, L-type Ca(2+)channel blocker nifedipine (1 micromol L(-1)), instead of Epiphany compounds, was assayed in adjacent rat aortic rings in parallel.
The catalyst and the mixture of Epiphany induced concentration-dependent relaxations. However, the base of Epiphany did not cause relaxation in rat aorta. The relaxation responses were not significantly altered by incubation of aorta with NOS, COX and potassium channel inhibitors. Whilst nifedipine, the catalyst and the mixture of Epiphany inhibited CaCl(2)-induced contractions (P < 0.05), the base of Epiphany did not inhibit CaCl(2)-induced contractions significantly (P > 0.05).
Epiphany induced relaxation of rat aorta via a calcium antagonistic effect. Provided that the vasodilatory effect elicited by Epiphany can be reversed by the circulation, its haemorrhagic potential by virtue of permanent vascular dilatation can be ignored.
验证 Epiphany（无论是混合形式还是单独成分）是否可以改变离体大鼠胸主动脉的血管反应这一假说。还研究了其血管作用的可能机制。
测试了 Epiphany 的碱、催化剂和混合物对预先用苯肾上腺素（PE）收缩的离体大鼠主动脉环的舒张作用。然后，将主动脉环用一氧化氮合酶（NOS）抑制剂、环氧化酶（COX）抑制剂或 K+通道抑制剂孵育；在用 PE 预收缩后，检查 Epiphany 的各种化合物的舒张作用。在另一组实验中，为了研究 Epiphany 的钙通道拮抗作用，检查了这些化合物在无钙溶液中对高 K+预刺激环（在 K+去极化环）中细胞外 Ca2+（CaCl2）诱导收缩的作用，以确定这些化合物的血管舒张作用是否直接抑制[Ca2+]内流增加。为了比较，在相邻的大鼠主动脉环中平行测定了 L 型钙通道阻滞剂硝苯地平（1 μmol L-1），而不是 Epiphany 化合物。
催化剂和 Epiphany 的混合物诱导了浓度依赖性的舒张。然而，Epiphany 的碱并没有引起大鼠主动脉的舒张。用 NOS、COX 和钾通道抑制剂孵育主动脉不会显著改变舒张反应。虽然硝苯地平、催化剂和 Epiphany 的混合物抑制了 CaCl2 诱导的收缩（P<0.05），但 Epiphany 的碱并没有显著抑制 CaCl2 诱导的收缩（P>0.05）。
Epiphany 通过钙拮抗作用引起大鼠主动脉舒张。如果 Epiphany 引起的血管舒张作用可以被循环逆转，那么它通过永久性血管扩张引起的出血潜力可以被忽略。
