硝苯地平和环匹阿尼酸对易卒中型肾性高血压大鼠血管平滑肌收缩功能的影响  

Effects of nifedipine and cyclopiazonic acid on contractility of vascular smooth muscle in stroke-prone renovascular hypertensive rats

作　　者：刘确[1,2] 关永源[1,2] 曾进胜[1,2] 贺华[1,2] 孙家钧[1,2] 

机构地区：[1]中山医科大学药理教研室 [2]中山医科大学附属第一医院神经内科

出　　处：《中国药理学与毒理学杂志》1996年第1期34-38,共5页Chinese Journal of Pharmacology and Toxicology

基　　金：国家自然科学基金;中山医科大学科学基金;香港求是科技基金

摘　　要：观察了易卒中型肾性高血压大鼠（ＳＰＲＨＲ）主动脉环血管平滑肌在术后血压升高不同阶段收缩反应性．与假手术组相比，随着术后血压的升高，低浓度ＫＣｌ１０～２０μｍｏｌ·Ｌ－１使ＳＰＲＨＲ主动脉环的收缩反应明显增强；苯肾上腺素（Ｐｈｅ）在无钙Ｋｒｅｂｓ液中所致的收缩反应强度降低，而复钙后的收缩张力明显增强；ＳＰＲＨＲ主动脉环在无钙Ｋｒｅｂｓ液中温育１ｈ后，重新复钙后可致收缩反应且为硝苯地平（Ｎｉｆ）所抑制；肌浆网Ｃａ２＋泵抑制剂环匹阿尼酸（ＣＰＡ）在ＳＰＲＨＲ主动脉环上所致的持续收缩反应也明显强于对照并为Ｎｉｆ所阻断；连续给予Ｎｉｆ，卡托普利１８０±１１ｍｇ·ｋｇ－１·ｄ－１８ｗｋ后，ＳＰＲＨＲ的血压均明显下降．在术后１，４ｗｋ，Ｎｉｆ对部分ＳＰＲＨＲ主动脉环在无钙液中复钙所致的收缩反应并无抑制作用且可进一步引起收缩反应．结果表明，肾性高血压大鼠血管平滑肌收缩功能的高反应性与高血压状态下Ｃａ２＋转运的失调有关，不同高血压时期的血管平滑肌细胞膜上的Ｃａ２＋通道特性可能存在差异性．Vascular responses of aortic rings from 2 kidney-2 clips, stroke-prone renovascular hypertensive Sprague-Dawley rats (SPRHRs) at different periods of post-clipping were compared to those of the age-matched normotensive SD rats. (1) The responses to cumulative concentration of KCl indicated that SPRHR aortic rings were hyperresponsive to low but not high concentration of KCl while being compared to normotensive controls. (2) For Phe-induced contraction, the contractile force of SPRHR aortic rings decreased significantly while being compared with age-matched normotensive controls in Ca 2+ -free solution containing EGTA. After Ca 2+ -repletion, the secondary contractile responses were significantly greater than those of controls. (3) After Ca 2+ -depletion by prolonged incubation of SPRHR aortic rings in Ca 2+ -free solution, the magnitude of such a contraction was dependent on the period of post-clipping and was highly sensitive to nifedipine (Nif), a dihydropyridine Ca 2+ channel blocker. In some cases of early renovascular hypertensive rats, however, it was found that Nif was able to induce further contraction. Such contractile responses were not observed in the control group. (4) The contractile response to cyclopiazonic acid (CPA) was significantly increased with the development of hypertension in SPRHRs. These responses in SPRHRs were more sensitive to Nif. However, the response to CPA in the control group was resistant to Nif. For SPRHRs at 1 wk of post-clipping, after given Nif or captopril in drinking water for 8 wk, the above abnormal reactivity was less potent while being compared with untreated group. Our findings suggest that vascular hyperreactivity in renovascular hypertension is related to an alteration in the transmembrane movement of Ca 2+ and intracellular Ca 2+ regulation; and during different periods of hypertension, the nature of the Ca 2+ channel on vascular smooth muscle may be different.

关 键 词：肾性高血压 硝基地平 环匹阿尼酸 血管平滑肌 

分 类 号：R972.4[医药卫生—药品] R544.14[医药卫生—药学]