Li J S, Schiffrin E L
MRC Multidisciplinary Research Group on Hypertension, Clinical Research Institute of Montréal, University of Montréal, Québec, Canada.
Am J Hypertens. 1997 Jan;10(1):94-100. doi: 10.1016/s0895-7061(96)00294-4.
Treatment of spontaneously hypertensive rats (SHR) and Wistar-Kyoto control rats (WKY) for at least 12 weeks with calcium channel antagonists is associated with regression of structural hypertensive changes in the heart and in conduit and small arteries. To establish whether structural or functional changes of small arteries could be corrected with shorter periods of specific antihypertensive treatment, SHR and WKY were treated for 4 weeks with the novel calcium channel blocker mibefradil. Blood pressure rise was significantly reduced by mibefradil treatment in SHR to 165 +/- 1 mm Hg compared to a systolic blood pressure of 183 +/- 2 mm Hg in untreated SHR (P <.01). Aortic hypertrophy in SHR was slightly reduced by treatment, but small artery hypertrophy in 4 vascular beds (mesenteric, renal, coronary, and femoral) was unaffected by administration of mibefradil for 4 weeks. Mibefradil treatment resulted in normalization of endothelium-dependent relaxation in mesenteric small arteries, with disappearance of acetylcholine-induced contractions, although hypertrophy and remodeling of these small arteries were not significantly affected by treatment. In WKY rats, treatment had no effect on either structure or function of small arteries. These results demonstrate that treatment with the calcium antagonist mibefradil may induce an improvement in altered endothelial function even before regression of cardiovascular hypertrophy and remodeling takes place under treatment, indicating that normalization of abnormal small artery endothelial function in SHR under antihypertensive therapy may be independent of correction of altered small artery structure.
用钙通道拮抗剂对自发性高血压大鼠（SHR）和Wistar - Kyoto对照大鼠（WKY）进行至少12周的治疗，与心脏以及大动脉和小动脉中结构性高血压变化的消退有关。为了确定较短时间的特定抗高血压治疗是否可以纠正小动脉的结构或功能变化，将SHR和WKY用新型钙通道阻滞剂米贝拉地尔治疗4周。与未治疗的SHR收缩压183±2 mmHg相比，米贝拉地尔治疗使SHR的血压升高显著降低至165±1 mmHg（P<.01）。治疗使SHR的主动脉肥厚略有减轻，但米贝拉地尔给药4周对4个血管床（肠系膜、肾、冠状动脉和股动脉）的小动脉肥厚没有影响。米贝拉地尔治疗使肠系膜小动脉的内皮依赖性舒张恢复正常，乙酰胆碱诱导的收缩消失，尽管这些小动脉的肥厚和重塑未受到治疗的显著影响。在WKY大鼠中，治疗对小动脉的结构和功能均无影响。这些结果表明，在用钙拮抗剂米贝拉地尔治疗时，甚至在治疗下心血管肥厚和重塑消退之前，就可能改善内皮功能改变，这表明在抗高血压治疗下SHR中小动脉异常内皮功能的恢复正常可能独立于小动脉结构改变的纠正。
