[Expressions of urotensin II and its receptor in pulmonary arteries in rats with chronic thromboembolic pulmonary hypertension].

ABSTRACT

OBJECTIVE: To investigate the expressions of Urotensin II (UII) protein and mRNA and its receptor (UT) mRNA of medium and small pulmonary arteries of rats with chronic thromboembolic pulmonary hypertension. METHODS: The Wistar rats were injected thrombi through the jugular vein 2 times in 2 weeks and tranexamic acid was injected peritoneally once daily during the experiment to prevent thrombolysis. The mean pulmonary artery pressure (mPAP) was measured using right cardiac atheterzation. The expressions of UII protein in pulmonary arteries were studied by immunohischemistry with a polycolonal antibody. The expressions of UII mRNA and UT mRNA were detected by in situ hybridization using UII and UT oligonuclear probes. The changes of structures in pulmonary vessle were observed, including relative medial thickness of pulmonary artery (PAMT) and vessle wall area/total vessle area (WA/TA). RESULTS: The mPAP of the 4 weeks to the 12 weeks groups were (19.9 +/- 6.2) mm Hg (1 mm Hg = 0.133 kPa), (23.8 +/- 4.1) mm Hg and (27.4 +/- 5.4) mm Hg, higher than that of the control group (F = 13.75, P < 0.01, respectively). The PAMT of the 4 weeks to the 12 weeks groups were (42.6 +/- 11.16)%, (47.82 +/- 10.02)% and (53.79 +/- 10.41)%, and WA/TA of the 4 weeks to the 12 weeks groups were (22.75 +/- 6.79)%, (25.32 +/- 4.90)% and (27.05 +/- 7.71)%, both changed significantly as compared to the control group (F = 5.52 and 6.61, P < 0.01, respectively; P < 0.05 in 4 weeks group; P < 0.01 in 8 weeks and 12 weeks groups, respectively). The expressions of UIIprotein, UII mRNA and UT mRNA in the 4 weeks to the 12 weeks groups were obviously higher than the control group (F = 30.39, 30.78 and 14.49, P < 0.01, respectively), and their expressions were more marked in the small pulmonary arteries than in medium pulmonary arteries. The expressions of UIIprotein, UII mRNA and UT mRNA were positively correlated with mPAP and PAMT. The pulmonary vascular remodeling was time-dependently aggravated after embolism (r 0.822, 0.866 and 0.846; 0.675, 0.712 and 0.756, P < 0.01, respectively). CONCLUSIONS: The expressions of UII protein, UII mRNA and UT mRNA of pulmonary arteries in the animal models were higher than those in the control group. These dynamic changes of UII mRNA, UIIprotein and UT mRNA may contribute to the development of pulmonary hypertension and vascular remodeling after pulmonary thromboembolism.