Turla M B, Park S M, Webb R C
Department of Physiology, University of Michigan Medical School, Ann Arbor 48109-0622.
J Hypertens. 1990 Feb;8(2):191-6. doi: 10.1097/00004872-199002000-00015.
Recent observations suggest that a phospholipid-sensitive, calcium-dependent protein kinase affects the contractile responses of vascular smooth muscle. Protein kinase C activators such as the tumor-promoting phorbol esters have been used as tools to study protein kinase C function in various intact cells. The present study characterizes vascular reactivity to protein kinase C activation in rats made hypertensive by coarctation of the abdominal aorta. Thoracic aortic strips from hypertensive rats developed greater force than arteries from normotensive rats in response to the phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA). Thoracic aortae from hypertensive rats were more responsive (lower threshold dose) to the phorbol ester than those from normotensive rats. Additionally, arteries from hypertensive rats were more responsive to the contractile effects of mezerein, a non-phorbol ester activator of protein kinase C. Removal of the endothelium did not eliminate the difference in responsiveness to TPA in thoracic aortae from normotensive and hypertensive rats. The threshold dose of TPA in abdominal aortae from hypertensive rats was not different from that in normotensive rats. However, the maximal response to 10(-6) mol/l TPA after 60 min in abdominal aortae from hypertensive rats was significantly less than that in aortae from normotensive rats. Thus, contractile responses to TPA appear to be influenced by arterial pressure per se. The inhibitory effects of the calcium antagonist, verapamil, in thoracic aortae from hypertensive rats were greater than in those from normotensive rats. Verapamil inhibited TPA-induced contractions in abdominal aortae from hypertensive rats to the same extent as in those from normotensive rats.(ABSTRACT TRUNCATED AT 250 WORDS)
近期观察结果表明，一种对磷脂敏感、依赖钙的蛋白激酶会影响血管平滑肌的收缩反应。蛋白激酶C激活剂，如具有促肿瘤作用的佛波酯，已被用作研究蛋白激酶C在各种完整细胞中功能的工具。本研究描述了腹主动脉缩窄致高血压大鼠中血管对蛋白激酶C激活的反应性。与正常血压大鼠的动脉相比，高血压大鼠的胸主动脉条对佛波酯12 - O - 十四烷酰佛波醇 - 13 - 乙酸酯（TPA）产生的力量更大。高血压大鼠的胸主动脉对佛波酯的反应性更强（阈值剂量更低）。此外，高血压大鼠的动脉对蛋白激酶C的非佛波酯激活剂蜂毒素的收缩作用反应更敏感。去除内皮并不能消除正常血压和高血压大鼠胸主动脉对TPA反应性的差异。高血压大鼠腹主动脉中TPA的阈值剂量与正常血压大鼠的无差异。然而，高血压大鼠腹主动脉在60分钟后对10(-6) mol/l TPA的最大反应明显小于正常血压大鼠的主动脉。因此，对TPA的收缩反应似乎受动脉压本身影响。钙拮抗剂维拉帕米对高血压大鼠胸主动脉的抑制作用大于对正常血压大鼠胸主动脉的抑制作用。维拉帕米对高血压大鼠腹主动脉TPA诱导的收缩的抑制程度与对正常血压大鼠腹主动脉的相同。（摘要截于250字）
