Black M J, Kanellakis P, Bobik A
Baker Medical Research Institute, Victoria, Australia.
J Hypertens. 1997 Sep;15(9):945-54. doi: 10.1097/00004872-199715090-00004.
To examine the role played by angiotensin II (AII) in the development of prehypertensive vascular hypertrophy in the spontaneously hypertensive rat (SHR) and to determine whether normalization of prehypertensive vascular hypertrophy attenuates the development of hypertension.
Male SHR and Wistar-Kyoto (WKY) rats were treated from age 10 days until age 6 weeks with perindopril, an angiotensin converting enzyme (ACE) inhibitor, or with losartan, a type 1 AII receptor antagonist.
At termination of treatment, or 8 weeks after cessation of treatment, vascular growth was assessed by measurement of hindquarter resistance properties and of the medial cross-sectional area of first-order mesenteric arteries. The growth of the heart was assessed by measurement of the left ventricle:body weight ratio.
Perindopril and losartan treatment of SHR and WKY rats led to a heterogeneous response in the vasculature, resulting in a reduction in perfusion pressures at maximum dilatation and constriction in the hindquarter vasculature but no significant change in medial cross-sectional area of small mesenteric arteries. Neither perindopril nor losartan treatment affected the growth of the left ventricle in the SHR. After the cessation of treatment the development of hypertension in the losartan- and perindopril-treated SHR did not differ from that in controls.
These results suggest that AII, acting via angiotensin type 1 receptors, plays an important role in determining the early post-natal reactivity of the hindquarter vasculature but not the medial cross-sectional area of the mesenteric vasculature, which implies that different growth regulatory mechanisms are operating in the two vascular beds. The lack of effect in some vascular beds, together with the lack of effect on the heart, may account for the absence of a persistent effect on the blood pressure.
研究血管紧张素II（AII）在自发性高血压大鼠（SHR）高血压前期血管肥厚发展过程中所起的作用，并确定高血压前期血管肥厚的正常化是否会减弱高血压的发展。
雄性SHR和Wistar-Kyoto（WKY）大鼠从10日龄开始至6周龄，分别用血管紧张素转换酶（ACE）抑制剂培哚普利或1型AII受体拮抗剂氯沙坦进行治疗。
在治疗结束时或停药8周后，通过测量后肢阻力特性和一级肠系膜动脉的中膜横截面积来评估血管生长情况。通过测量左心室与体重比来评估心脏的生长情况。
培哚普利和氯沙坦对SHR和WKY大鼠的治疗导致血管系统出现异质性反应，使得后肢血管系统在最大扩张和收缩时的灌注压力降低，但小肠系膜动脉的中膜横截面积没有显著变化。培哚普利和氯沙坦治疗均未影响SHR左心室的生长。停药后，氯沙坦和培哚普利治疗的SHR的高血压发展与对照组无差异。
这些结果表明，AII通过1型血管紧张素受体发挥作用，在决定出生后早期后肢血管系统的反应性方面起重要作用，但对肠系膜血管系统的中膜横截面积不起作用，这意味着两个血管床存在不同的生长调节机制。在某些血管床缺乏作用，以及对心脏缺乏作用，可能是对血压没有持续影响的原因。
