Chen D G, Jin X Q, Wang H J, Chen S C
Hypertension Division, First Affiliated Hospital, Fujian Medical College, Fuzhou, People's Republic of China.
J Hypertens. 1995 Oct;13(10):1113-21. doi: 10.1097/00004872-199510000-00006.
To investigate new aspects of the relationship between sustained reduction of blood pressure and alteration of cardiovascular structure and function after cessation of early captopril treatment.
Spontaneously hypertensive rats (SHR) were given captopril 20 mg/kg per day (n = 13) or 100 mg/kg per day (n = 12) from the intra-uterine period to age 16 weeks and then the treatment was stopped. Age-matched untreated SHR (n = 16) and Wistar-Kyoto (WKY) rats (n = 17) served as controls. The experiments were carried out at 40 weeks.
Withdrawal of captopril treatment resulted in a rapid rebound of SBP to a level close to that of untreated SHR in the low-dose group, whereas a persistently lower SBP was maintained in the high-dose group. Both doses of captopril treatment completely prevented wall hypertrophy either of arteriolar resistance vessels or of muscular vessels. Captopril decreased left ventricular mass:body weight ratio dose-dependently. High-dose captopril improved the resting and stress systolic and diastolic function. Thoracic angiotensin converting enzyme levels were dose-dependently reduced by captopril treatment. The curves of perfusion pressure response to incremental doses of phenylephrine shifted to the right in both captopril treatment groups compared with those of the control SHR. Addition of L-NAME and L-arginine to the perfusate augmented or attenuated the vasoconstrictor activity in all of the rats, whereas high-dose captopril totally restored the abnormal hypersensitivity to L-NAME and caused less attenuation in response to L-arginine in the control SHR.
The persistent lower blood pressure caused by early captopril treatment was ascribed mainly to its sustained normalization of structure and function of resistance vessels, which may be partly mediated by the improvement of endothelial cell function. The persistent reduction of angiotensin converting enzyme activity in blood vessel wall attenuated left ventricular hypertrophy, and the improvement of cardiac systolic and diastolic function may also contribute to the sustained hypotensive effect.
探讨早期卡托普利治疗停止后血压持续降低与心血管结构和功能改变之间关系的新方面。
自发性高血压大鼠（SHR）从子宫内期至16周龄每天给予卡托普利20mg/kg（n = 13）或100mg/kg（n = 12），然后停止治疗。年龄匹配的未治疗SHR（n = 16）和Wistar-Kyoto（WKY）大鼠（n = 17）作为对照。实验在40周时进行。
低剂量组停用卡托普利治疗导致收缩压迅速反弹至接近未治疗SHR的水平，而高剂量组收缩压持续维持在较低水平。两种剂量的卡托普利治疗均完全预防了小动脉阻力血管和肌性血管的壁肥厚。卡托普利剂量依赖性地降低左心室质量：体重比。高剂量卡托普利改善静息和应激状态下的收缩和舒张功能。卡托普利治疗使胸段血管紧张素转换酶水平呈剂量依赖性降低。与对照SHR相比,两个卡托普利治疗组对去氧肾上腺素递增剂量的灌注压反应曲线均右移。向灌注液中添加L- NAME和L-精氨酸增强或减弱了所有大鼠的血管收缩活性，而高剂量卡托普利完全恢复了对照SHR对L- NAME的异常高敏性，且对L-精氨酸的反应减弱较少。
早期卡托普利治疗导致的持续低血压主要归因于其使阻力血管结构和功能持续正常化，这可能部分由内皮细胞功能改善介导。血管壁中血管紧张素转换酶活性的持续降低减轻了左心室肥厚，心脏收缩和舒张功能的改善也可能有助于持续的降压作用。
