Rabinovitch M, Mullen M, Rosenberg H C, Maruyama K, O'Brodovich H, Olley P M
Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada.
Am J Physiol. 1988 Mar;254(3 Pt 2):H500-8. doi: 10.1152/ajpheart.1988.254.3.H500.
Angiotensin II, a vasoconstrictor, has been previously demonstrated to produce a secondary vasodilatation due to release of prostaglandins. Because of this effect, we investigated whether infusion of exogenous angiotensin II via miniosmopumps in rats during a 1-wk exposure to chronic hypobaric hypoxia might prevent pulmonary hypertension, right ventricular hypertrophy, and vascular changes. We instrumented the rats with indwelling cardiovascular catheters and compared the hemo-dynamic and structural response in animals given angiotensin II, indomethacin in addition to angiotensin II (to block prostaglandin production), or saline with or without indomethacin. We then determined whether angiotensin II infusion also prevents acute hypoxic pulmonary vasoconstriction. We observed that exogenous angiotensin II infusion abolished the rise in pulmonary artery pressure, the right ventricular hypertrophy, and the vascular changes induced during chronic hypoxia in control saline-infused rats with or without indomethacin. The protective effect of angiotensin II was lost when indomethacin was given to block prostaglandin synthesis. During acute hypoxia, both angiotensin II and prostacyclin infusions similarly prevented the rise in pulmonary artery pressure observed in saline-infused rats and in rats given indomethacin or saralasin in addition to angiotensin II. Thus exogenous angiotensin II infusion prevents chronic hypoxic pulmonary hypertension, associated right ventricular hypertrophy, and vascular changes and blocks acute hypoxic pulmonary hypertension, and this is likely related to its ability to release vasodilator prostaglandins.
血管紧张素II是一种血管收缩剂，先前已证明它会因前列腺素的释放而产生继发性血管舒张。鉴于这种作用，我们研究了在大鼠为期1周的慢性低压缺氧暴露期间，通过微型渗透泵输注外源性血管紧张素II是否可以预防肺动脉高压、右心室肥大和血管变化。我们给大鼠植入了留置心血管导管，并比较了给予血管紧张素II、除血管紧张素II外还给予吲哚美辛（以阻断前列腺素生成）或给予含或不含吲哚美辛的生理盐水的动物的血流动力学和结构反应。然后我们确定血管紧张素II输注是否也能预防急性低氧性肺血管收缩。我们观察到，外源性血管紧张素II输注消除了在输注含或不含吲哚美辛的对照生理盐水的大鼠慢性缺氧期间诱导的肺动脉压升高、右心室肥大和血管变化。当给予吲哚美辛以阻断前列腺素合成时，血管紧张素II的保护作用丧失。在急性缺氧期间，血管紧张素II和前列环素输注同样预防了在输注生理盐水的大鼠以及除血管紧张素II外还给予吲哚美辛或沙拉新的大鼠中观察到的肺动脉压升高。因此，外源性血管紧张素II输注可预防慢性低氧性肺动脉高压、相关的右心室肥大和血管变化，并阻断急性低氧性肺动脉高压，这可能与其释放血管舒张性前列腺素的能力有关。
