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[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).


CONCLUSION
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.