AN ANTIFIBROTIC AGENT REDUCES BLOOD-PRESSURE IN ESTABLISHED PULMONARY-HYPERTENSION IN THE RAT

被引:25
作者
POIANI, GJ
TOZZI, CA
CHOE, JK
YOHN, SE
RILEY, DJ
机构
[1] UNIV MED & DENT NEW JERSEY,ROBERT WOOD JOHNSON MED SCH,DEPT MED,NEW BRUNSWICK,NJ 08903
[2] VET ADM MED CTR,DEPT PATHOL,LYONS,NJ 07939
关键词
blood viscosity; cis-hydroxyproline; connective tissue; proline analogue; pulmonary circulation;
D O I
10.1152/jappl.1990.68.4.1542
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
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 in arterioles. Treatment reduced right ventricular pressure from 21 ± 1 to 17 ± 1 mmHg (P < 0.05), hematocrit from 66 ± 1 to 56 ± 1% (P < 0.05), hydroxyproline content of intrapulmonary arteries from 30 ± 3 to 11 ± 2 μg/vessel (P < 0.05), and wall thickness from 27 ± 3 to 16 ± 2 μm (P < 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.
引用
收藏
页码:1542 / 1547
页数:6
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