[Preventive effects of montelukast on hypoxic pulmonary hypertension in rats].
OBJECTIVE
To evaluate the role of cysteinyl leukotriene(CysLT) in the pathogenesis of hypoxic pulmonary hypertension and the preventive effects of montelukast, a CysLT receptor antagonist, on hypoxic pulmonary hypertension.


METHODS
Thirty male Wistar rats were randomly divided into three groups: control group, hypoxic group and montelukast preventive group. The animal model of pulmonary hypertension was established by exposing the rats to normabaric hypoxic conditions for 3 weeks. The thickness of pulmonary arterioles was measured by a computerized image analyzer. The level of LTC4 in plasma was measured by EIA.


RESULTS
In the hypoxic group, the index of right ventricular hypertrophy[RV/(LV + S)] and the index of wall thickness of pulmonary arteriole (WT% and WA%) increased significantly when compared against those in the control group [RV/(LV + S): 30.85% +/- 1.44% vs 20.75% +/- 1.97%; WT%: 23.54% +/- 4.43% vs 13.17% +/- 3.67%; WA%: 72.76% +/- 9.28% vs 50.41% +/- 6.37%, P < 0.01, respectively]. Meanwhile, the plasma level of LTC4 in hypoxic rats was higher than that in control rats [(2395.40 +/- 193.86) pg/ml vs (1006.50 +/- 193.17) pg/ml, P < 0.01]. In the preventive group, the RV/(LV + S) (24.09% +/- 1.09%), WT% (15.44% +/- 4.72%) and WA% (51.98% +/- 12.18%) decreased remarkably as compared with those of the hypoxic group(P < 0.01). The plasma level of LTC4 in the preventive group (2706.25 +/- 350.49 pg/ml) was not significantly different from that in the hypoxic group(P > 0.05).


CONCLUSIONS
Chronic hypoxia stimulates synthesis and release of LTC4. CysLT may play an important role in the pathogenesis of hypoxic pulmonary hypertension and montelukast can prevent hypoxi pulmonary hypertension.
Chen
Xiaoju
X
Department of Respiratory Medicine, West China Hospital, Sichuan University, Chengdu 610041, China.
Cheng
Deyun
D
Guan
Jian
J
Xia
Xiuqiong
X
Fan
Lili
L
Su
Qiaoli
Q
D000085:Acetates / Q000494:pharmacology*; D000818:Animals; D003521:Cyclopropanes; D006976:Hypertension, Pulmonary / Q000209:etiology / Q000517:prevention & control*; D000860:Hypoxia / Q000150:complications*; D020024:Leukotriene Antagonists / Q000494:pharmacology*; D017997:Leukotriene C4 / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000037:antagonists & inhibitors; D011804:Quinolines / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D018077:Receptors, Leukotriene; D013440:Sulfides
D000085:Acetates; D003521:Cyclopropanes; D020024:Leukotriene Antagonists; D008565:Membrane Proteins; D011804:Quinolines; D018077:Receptors, Leukotriene; D013440:Sulfides; D017997:Leukotriene C4; C083169:leukotriene D4 receptor; C093875:montelukast