Simon G, Abraham G, Altman S
Department of Medicine, VA Medical Center, Minneapolis, MN 55417.
Hypertension. 1994 Jan;23(1 Suppl):I148-51. doi: 10.1161/01.hyp.23.1_suppl.i148.
The vascular trophic effects of angiotensin II (Ang II) in small doses may precede its hypertension-producing effect, and de novo synthesis of components of extracellular matrix may be a requirement for Ang II-stimulated growth. In the present study, therefore, the incorporation of 35SO4 into glycosaminoglycans (synthesis) of aorta and bladder wall of young adult, male Sprague-Dawley rats was measured ex vivo after 48 hours of Ang II administration at two dose levels, 100 and 200 ng.kg-1.min-1 IP. Vehicle-infused rats served as controls. Compared with controls, systolic blood pressure was unchanged in rats receiving 100 ng.kg-1.min-1 Ang II and rose by 13 mm Hg (P < .05) in rats receiving the 200-ng.kg-1.min-1 dose. In Ang II-treated rats, glycosaminoglycan synthesis of the aorta was increased by 20% (P < .05) and 52% (P < .005) at the two dose levels, respectively. Glycosaminoglycan synthesis of bladder smooth muscle was also increased in Ang II-treated rats (P < .01), but the response was not dose dependent. By 7 to 10 days of Ang II administration (200 ng.kg-1.min-1), glycosaminoglycan synthesis of aorta returned toward baseline (P < .10, > .05). The rate of synthesis of subtypes of glycosaminoglycans in the aorta was proportionately increased by Ang II. The early occurrence, magnitude, and arterial pressure independence of Ang II-induced glycosaminoglycan synthesis suggest that restructuring of extracellular matrix may play an important role in both the trophic and hypertension-producing action of Ang II.
小剂量血管紧张素II(Ang II)的血管营养作用可能先于其产生高血压的作用,细胞外基质成分的从头合成可能是Ang II刺激生长的必要条件。因此,在本研究中,对年轻成年雄性Sprague-Dawley大鼠腹腔注射100和200 ng.kg-1.min-1两种剂量水平的Ang II 48小时后,离体测定其主动脉和膀胱壁中35SO4掺入糖胺聚糖(合成)的情况。输注溶媒的大鼠作为对照。与对照组相比,接受100 ng.kg-1.min-1 Ang II的大鼠收缩压未改变,而接受200 ng.kg-1.min-1剂量的大鼠收缩压升高了13 mmHg(P <.05)。在接受Ang II治疗的大鼠中,主动脉糖胺聚糖合成在两个剂量水平分别增加了20%(P <.05)和52%(P <.005)。接受Ang II治疗的大鼠膀胱平滑肌糖胺聚糖合成也增加(P <.01),但反应不依赖剂量。给予Ang II(200 ng.kg-1.min-1)7至10天后,主动脉糖胺聚糖合成恢复至基线水平(P <.10,>.05)。Ang II使主动脉中糖胺聚糖亚型的合成速率成比例增加。Ang II诱导的糖胺聚糖合成的早期发生、幅度和与动脉压无关表明,细胞外基质的重构可能在Ang II的营养作用和产生高血压作用中都起重要作用。