Black M J, Bertram J F, Campbell J H, Campbell G R
Department of Medicine, University of Melbourne, Heidelberg, Victoria, Australia.
J Hypertens. 1995 Jun;13(6):683-92. doi: 10.1097/00004872-199506000-00016.
To investigate whether angiotensin II (Ang II) exerts a direct effect on cardiovascular hypertrophy in the spontaneously hypertensive rat or acts indirectly through elevation of blood pressure.
Immature (7-week-old) and mature (14-week-old) spontaneously hypertensive rats were treated for 8 and 6 weeks, respectively, with an angiotensin converting enzyme inhibitor to block the in vivo production of Ang II and concomitantly infused with either a pressor dose of Ang II or noradrenaline.
At the termination of treatment, vascular smooth muscle cell growth was assessed in the aorta and mesenteric arterioles.
In the young rats systolic blood pressure was not significantly different in the Ang II- and noradrenaline-infused groups. In the mature rats blood pressure was elevated in the Ang II-infused rats above that in the untreated and noradrenaline-infused groups, in which blood pressure was not significantly different. Ang II infusion induced cardiac hypertrophy and medial hypertrophy both in the aorta and in first-order mesenteric arterioles, accompanied by induction of smooth muscle polyploidy. The growth response to Ang II differed in the large and small vessels, with a marked induction of smooth muscle hyperplasia in the mesenteric arterioles but no change in cell number in the aorta. Infusion of noradrenaline did not induce cardiac or vascular hypertrophy, levels being similar to those in the rats treated with perindopril only.
These results suggest that Ang II can directly stimulate cardiac and vascular hypertrophy in the spontaneously hypertensive rat, independently of its effect on blood pressure.
研究血管紧张素II（Ang II）对自发性高血压大鼠的心血管肥大是产生直接作用，还是通过升高血压间接发挥作用。
分别用血管紧张素转换酶抑制剂对未成熟（7周龄）和成熟（14周龄）的自发性高血压大鼠进行8周和6周的治疗，以阻断Ang II的体内生成，同时分别输注升压剂量的Ang II或去甲肾上腺素。
在治疗结束时，评估主动脉和肠系膜小动脉中血管平滑肌细胞的生长情况。
在幼鼠中，输注Ang II组和输注去甲肾上腺素组的收缩压无显著差异。在成年大鼠中，输注Ang II组的血压高于未治疗组和输注去甲肾上腺素组，而后两组的血压无显著差异。输注Ang II可诱导心脏肥大以及主动脉和一级肠系膜小动脉的中膜肥大，并伴有平滑肌多倍体的诱导。对Ang II的生长反应在大血管和小血管中有所不同，肠系膜小动脉中平滑肌增生明显诱导，但主动脉中的细胞数量无变化。输注去甲肾上腺素未诱导心脏或血管肥大，其水平与仅用培哚普利治疗的大鼠相似。
这些结果表明，Ang II可直接刺激自发性高血压大鼠的心脏和血管肥大，而与其对血压的影响无关。
