Dilley R J, Nataatmadja M I
Morphology Laboratory, Baker Medical Research Institute, Victoria, Australia.
Cardiovasc Res. 1998 Apr;38(1):247-55. doi: 10.1016/s0008-6363(98)00004-2.
Chronic infusion with angiotensin II increases blood pressure and activates growth mechanisms to produce hypertrophy of the heart and vessels. In order to better understand mechanisms of angiotensin II induced vascular hypertrophy, this study aimed to determine whether heparin, a potent inhibitor of smooth muscle proliferation mechanisms, was able to inhibit vascular hypertrophy.
Angiotensin II (100, 200 or 300 ng/min/kg s.c.) or a saline vehicle control were infused into rats for 14 days. A separate group of animals were co-infused with heparin (0.3 mg/h/kg i.v.) and angiotensin II (200 ng/min/kg s.c.) to test whether hypertension or hypertrophy were antagonized. Blood pressure was measured by tail cuff method and vessel media cross sectional area was measured by morphometry in aorta and mesenteric arteries.
Blood pressure elevation and cardiovascular hypertrophy produced by angiotensin II were strongly dose-dependent. Hypertrophy responses at 14 days of treatment also appeared to be influenced partly by local factors as medial cross sectional area was increased more in mesenteric arteries than in thoracic aorta, and left ventricle weight was least affected. Heparin treatment did not influence the increase of blood pressure in angiotensin II infused animals, but the mesenteric vascular hypertrophy response due to angiotensin II was inhibited by approximately 50%. Inhibition of a modest cardiac hypertrophy and aortic medial hypertrophy did not reach significance.
Angiotensin II infusion produced vascular medial hypertrophy and increased blood pressure, however the inhibitory effect of heparin on hypertrophy in mesenteric arteries was not mediated through angiotensin II induced vasoconstriction or blood pressure elevation. These data suggest that heparin interferes directly with the hypertrophy mechanism in mesenteric arteries, and that heparin-sensitive growth mechanisms are important in mediating angiotensin induced mesenteric vascular hypertrophy.
长期输注血管紧张素II可升高血压并激活生长机制，导致心脏和血管肥大。为了更好地理解血管紧张素II诱导血管肥大的机制，本研究旨在确定肝素（一种平滑肌增殖机制的有效抑制剂）是否能够抑制血管肥大。
将血管紧张素II（100、200或300 ng/分钟/千克，皮下注射）或生理盐水载体对照注入大鼠体内14天。另一组动物同时输注肝素（0.3毫克/小时/千克，静脉注射）和血管紧张素II（200 ng/分钟/千克，皮下注射），以测试高血压或肥大是否被拮抗。通过尾袖法测量血压，通过形态测量法测量主动脉和肠系膜动脉的血管中膜横截面积。
血管紧张素II引起的血压升高和心血管肥大具有强烈的剂量依赖性。治疗14天时的肥大反应似乎也部分受局部因素影响，因为肠系膜动脉的中膜横截面积增加幅度大于胸主动脉，而左心室重量受影响最小。肝素治疗并未影响输注血管紧张素II的动物的血压升高，但血管紧张素II引起的肠系膜血管肥大反应被抑制了约50%。对轻度心脏肥大和主动脉中膜肥大的抑制作用未达到显著水平。
输注血管紧张素II可导致血管中膜肥大并升高血压，然而肝素对肠系膜动脉肥大的抑制作用并非通过血管紧张素II诱导的血管收缩或血压升高介导。这些数据表明，肝素直接干扰肠系膜动脉的肥大机制，并且肝素敏感的生长机制在介导血管紧张素诱导的肠系膜血管肥大中起重要作用。
