Forster C
Department of Medicine, University of Toronto, ON, Canada.
Can J Physiol Pharmacol. 1995 May;73(5):651-60. doi: 10.1139/y95-083.
Contractions of the dorsal pedal artery and saphenous vein to phorbol 12,13-dibutyrate (PDBu), 12-O-tetradecanoylphorbol 13-acetate (TPA), and 4 alpha-phorbol 12,13-didecanoate (4 alpha-phorbol) were measured from dogs with and without pacing-induced heart failure. The effects of polymyxin B (a relatively selective protein kinase C inhibitor), nifedipine (calcium channel blocker), and prazosin (alpha 1-adrenoceptor antagonist) were examined on the contractions developed to PDBu before heart failure, after 1 week of pacing, and at end-stage heart failure. PDBu and TPA, but not 4 alpha-phorbol, produced concentration-dependent increases in contractile force in both the artery and the vein. In the dorsal pedal artery, efficacy of and sensitivity to PDBu and TPA were enhanced after 1 week of pacing, but returned to control level at end-stage heart failure. In the saphenous vein, the concentration-effect curve to PDBu was displaced to the left after 1 week of pacing; EC50 values for PDBu were 3.2 x 10(-9) and 3.2 x 10(-8) M for 1 week paced and control, respectively. Polymyxin B significantly decreased the efficacy of PDBu in the dorsal pedal artery at all time points, but was less effective with advancing heart failure. In contrast, in the vein, there was a significant increase in inhibitory potential at end-stage heart failure. In all cases, nifedipine inhibited PDBu in a concentration-dependent manner. With the progression of heart failure, the contractions of the saphenous vein, developed to PDBu, became more sensitive to inhibition by nifedipine. Prazosin failed to inhibit vascular effects of PDBu. These results are discussed in terms of protein kinase C involvement in vascular contractions and its role in the pathogenesis of heart failure.
在有或没有起搏诱导性心力衰竭的犬中，测量了足背动脉和大隐静脉对佛波醇12,13 - 二丁酸酯（PDBu）、12 - O - 十四酰佛波醇13 - 乙酸酯（TPA）和4α - 佛波醇12,13 - 二癸酸酯（4α - 佛波醇）的收缩反应。研究了多粘菌素B（一种相对选择性的蛋白激酶C抑制剂）、硝苯地平（钙通道阻滞剂）和哌唑嗪（α1 - 肾上腺素能受体拮抗剂）对心力衰竭前、起搏1周后和终末期心力衰竭时对PDBu产生的收缩反应的影响。PDBu和TPA，但不是4α - 佛波醇，在动脉和静脉中均产生浓度依赖性的收缩力增加。在足背动脉中，起搏1周后PDBu和TPA的效力和敏感性增强，但在终末期心力衰竭时恢复到对照水平。在大隐静脉中，起搏1周后对PDBu的浓度 - 效应曲线向左移位；起搏1周和对照时PDBu的半数有效浓度（EC50）值分别为3.2×10−9和3.2×10−8 M。多粘菌素B在所有时间点均显著降低足背动脉中PDBu的效力，但随着心力衰竭进展其作用减弱。相反，在静脉中，终末期心力衰竭时抑制潜能显著增加。在所有情况下，硝苯地平以浓度依赖性方式抑制PDBu。随着心力衰竭的进展，大隐静脉对PDBu产生的收缩反应对硝苯地平的抑制变得更加敏感。哌唑嗪未能抑制PDBu的血管效应。根据蛋白激酶C参与血管收缩及其在心力衰竭发病机制中的作用对这些结果进行了讨论。
