Storm D S, Turla M B, Todd K M, Webb R C
Department of Physiology, University of Michigan Medical School, Ann Arbor 48109-0622.
Am J Hypertens. 1990 Aug;3(8 Pt 2):245S-248S. doi: 10.1093/ajh/3.8.245.
This study examined the calcium dependency of contractions in arteries from rats made hypertensive by aortic coarctation and in rats with genetic hypertensive (stroke-prone spontaneously hypertensive rats). Mesenteric artery and aortic strips were suspended in tissue baths for isometric force recording and contractions to two drugs were characterized: 1) a phorbol ester, TPA (12-O-tetrade-canoylphorbol-13-acetate), and 2) the calcium channel agonist, Bay K 8644. Thoracic aortae and mesenteric arteries from hypertensive rats were more sensitive to the contractile properties of the protein kinase C activator TPA than comparable arteries from normotensive rats. In thoracic aortae from coarcted rats, the contractile activity of Bay K 8644 was potentiated compared to normotensive values. In the presence of 19.2 mmol/L KCl, responses to Bay K 8644 in thoracic aortae from normotensive rats were potentiated and did not differ from coarcted values. In contrast, contractions to Bay K 8644 and TPA in abdominal aortae obtained below the coarctation were not different from normotensive values. Upon exposure to 26.2 mmol/L KCl, contractions to Bay K 8644 in abdominal aortae were potentiated and those in aortae from coarcted rats did not differ from sham values. Contractile responses to both drugs were blocked by nifedipine and verapamil and responses were attenuated in calcium-free solution. We conclude that calcium channel function and its regulation by protein kinase C contribute to altered vascular reactivity in hypertension. Further, these abnormalities have a pressure dependency, because they did not occur in abdominal aortae from coarcted rats.
本研究检测了经主动脉缩窄形成高血压的大鼠以及遗传性高血压大鼠（易卒中型自发性高血压大鼠）动脉收缩的钙依赖性。将肠系膜动脉和主动脉条悬挂于组织浴槽中进行等长力记录，并对两种药物引起的收缩进行了表征：1）佛波酯，TPA（12 - O - 十四烷酰佛波醇 - 13 - 乙酸酯），以及2）钙通道激动剂，Bay K 8644。高血压大鼠的胸主动脉和肠系膜动脉对蛋白激酶C激活剂TPA的收缩特性比正常血压大鼠的相应动脉更敏感。与正常血压值相比，缩窄大鼠胸主动脉中Bay K 8644的收缩活性增强。在19.2 mmol/L KCl存在下，正常血压大鼠胸主动脉对Bay K 8644的反应增强，且与缩窄大鼠的值无差异。相反，缩窄下方获得的腹主动脉对Bay K 8644和TPA的收缩与正常血压值无差异。暴露于26.2 mmol/L KCl时，腹主动脉对Bay K 8644的收缩增强，缩窄大鼠主动脉的收缩与假手术组的值无差异。两种药物的收缩反应均被硝苯地平和维拉帕米阻断，且在无钙溶液中反应减弱。我们得出结论，钙通道功能及其受蛋白激酶C的调节促成了高血压中血管反应性的改变。此外，这些异常具有压力依赖性，因为它们在缩窄大鼠的腹主动脉中未出现。
