Treatment of pulmonary hypertension by retinoid

雄性Sprague-Dawley大鼠在单次皮下注射野百合碱（60 mg/kg）或生理盐水后，于注射前2天和注射后17天分别灌胃给予羧甲基纤维素载体或载体中的30 mg/kg全反式维甲酸。在戊巴比妥钠麻醉下，静滴野百合碱17天后，置入肺动脉导管。于插管后48小时测定大鼠全意识肺动脉压（PAP）。然后进行定量形态学分析，其中通过光学显微镜评估正常非肌性外周肺动脉的肌化和正常肌性动脉的中膜肥大。野百合碱引起PAP升高和高血压肺血管改变。本研究中使用的全反式维甲酸并没有阻止或放大的发展，PH，右心室肥大，中层肥大的肌动脉或新的周围动脉肌化野百合碱诱导的PH。血浆中的全反式维甲酸水平较高，灌胃全反式维甲酸大鼠。总之，ATRA（30 mg/kg/d）不能阻止野百合碱诱导的PH中高血压血管改变的发展。

Male Sprague-Dawley rats were given 30mg/kg ATRA in a carboxymethylcellulose vehicle or vehicle only by gavage, 2 days before and once daily for 17days after a single subcutaneous injection of either monocrotaline (60mg/kg) or saline. Indwelling pulmonary artery catheter was inserted under the pentobarbital anesthesia after 17 days of monocrotaline. Fourty eight hours after the catheterization with the rat fully conscious pulmonary artery pressure (PAP) was measured. Then quantitative morphometric analysis was carried out, in which muscularization of normally nonmuscular peripheral pulmonary arteries and medial hypertrophy of normally muscular arteries were assessed by light microscopy. Monocrotaline induced rise in PAP and hypertensive pulmonary vascular changes. ATRA used in the present study did not prevent nor magnify the development of PH, right ventricular hypertrophy, medial hypertrophy of muscular arteries or new muscularization of peripheral arteries in monocrotaline-induced PH. Plasma ATRA level was higher in rats gavaged with ATRA. In summary, administration of ATRA (30mg/kg/day) could not prevent the development of hypertensive vascular changes in monocrotaline-induced PH.