[Gα11 expression and effect of sildenafil in muscularization of non-muscular pulmonary arterioles in rat with pulmonary arterial hypertension].

OBJECTIVE

To investigate expression changes and role of Gα11 protein in the processes of muscularization of non-muscular pulmonary arterioles and effect of sildenafil intervention in rats with pulmonary arterial hypertension (PAH).

METHODS

Thirty SD rats were randomly divided into three groups, including normal control group, monocrotaline (MCT) group and sildenafil group; PAH model was prepared with 50 mg/kg MCT treatment for 4 weeks in the MCT group, and these rats were treated by 25 mg/kg sildenafil for 2 weeks after PAH formation in the sildenafil group, and the normal control group were treated with the equal amounts of physiological saline instead of monocrotaline; pulmonary artery pressure was measured with jugular vein catheterization; hematoxylin and eosin (HE) staining method was used to detect the pulmonary arteriolar morphology and vascular tissue parameters; expression of the target Gα11 protein, vascular smooth muscle marker osteopontin (OPN) and proliferation marker proliferating cell nuclear antigen (PCNA) was detected by Western blot.

RESULTS

Pulmonary artery mean pressure (mPAP), non-muscular pulmonary arterioles wall thickness index (TI) and area index (AI) of the MCT group were higher than those of the normal control group[(27.43±3.97) vs (11.93±1.52) mmHg (1 mmHg=0.133 kPa), 0.49±0.07 vs 0.31±0.09 and 0.74±0.05 vs 0.45±0.10](all P<0.05), and meanwhile the expression levels of Gα11 and the related proteins including OPN and PCNA were significantly enhanced. mPAP, TI and AI[(18.59±1.44) mmHg, 0.39±0.09 and 0.56±0.04]of the sildenafil group were all lower than those of the MCT group (all P<0.05), and furthermore, expressions of Gα11, OPN and PCNA also reduced in line with these changes.

CONCLUSION

Gα11 protein plays a role in the development of PAH and pulmonary non-muscular arteriole muscularization, and sildenafil effectively suppresses PAH and pulmonary vascular remodeling by inhibiting Gα11 expression.