An antifibrotic agent reduces blood pressure in established pulmonary hypertension in the rat.
An antifibrotic agent reduces blood pressure in established pulmonary hypertension in the rat.
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DOI：
10.1152/jappl.1990.68.4.1542
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发表时间：
1990-04
影响因子：
3.3
通讯作者：
G. Poiani;C. Tozzi;J. K. Choe;S. Yohn;D. Riley
中科院分区：
文献类型：
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作者：
G. Poiani;C. Tozzi;J. K. Choe;S. Yohn;D. Riley
我们已经表明，在暴露于缺氧的大鼠开始时给予抗纤维化剂顺式-4-羟基-L-脯氨酸（cHyp）可以防止肺动脉中胶原蛋白的积累和肺血压的升高。在这个实验中，我们测试了在已经建立高血压之后施用cHyp是否有效。大鼠暴露于缺氧（10%O2）21天。组是在第10 - 21天用cHyp（200 mg/kg sc，每日两次）处理的缺氧动物（缺氧cHyp）和盐水注射的缺氧动物（缺氧）。在第21天，我们测量了平均右心室压力，红细胞压积，主动脉和肺内动脉的胶原含量，以及小动脉壁厚度。治疗使右心室压力从21 +/-1 mmHg降至17 +/-1 mmHg（P <0.05），红细胞压积从66 +/-1至56 +/-1%（P小于0.05），肺内动脉的羟脯氨酸含量为30 +/-3至11 +/-2微克/血管（P小于0.05），壁厚为27 +/-3至16 +/-2微米（P小于0.05）。这些结果表明，在建立的肺动脉高压中血管胶原蛋白含量增加，并且如果在建立肺动脉高压后开始，cHyp治疗在部分预防血液动力学、结构和生化变化方面是有效的。cHyp也可能影响血液的流变学性质。
We have shown that administration of the antifibrotic agent cis-4-hydroxy-L-proline (cHyp) to rats at the onset of exposure to hypoxia prevents collagen accumulation in pulmonary arteries and the rise in pulmonary blood pressure. In this experiment, we tested whether cHyp is effective when administered after hypertension was already established. Rats were exposed to hypoxia (10% O2) for 21 days. Groups were hypoxic animals treated with cHyp (200 mg/kg sc twice daily) on days 10-21 (hypoxic cHyp) and saline-injected hypoxic animals (hypoxic). On day 21, we measured mean right ventricular pressure, hematocrit, collagen content of main and intrapulmonary arteries, and wall thickness of arterioles. Treatment reduced right ventricular pressure from 21 +/- 1 to 17 +/- 1 mmHg (P less than 0.05), hematocrit from 66 +/- 1 to 56 +/- 1% (P less than 0.05), hydroxyproline content of intrapulmonary arteries from 30 +/- 3 to 11 +/- 2 micrograms/vessel (P less than 0.05), and wall thickness from 27 +/- 3 to 16 +/- 2 microns (P less than 0.05). These results show that vascular collagen content is increased in established pulmonary hypertension and that cHyp treatment is effective in partially preventing the hemodynamic, structural, and biochemical changes if started after pulmonary hypertension is established. cHyp may also affect the rheological properties of blood.