Effect of sildenafil on expression of hexokinase-2 in lung tissues in a rat model of Hypertension, pul-monary / 中华麻醉学杂志

ABSTRACT

Objective To evaluate the effect of sildenafil on the expression of hexokinase-2 (HK-2) in lung tissues in a rat model of pulmonary arterial hypertension. Methods Thirty-two male Sprague-Dawley rats, aged 2 months, weighing 200-220 g, were allocated into 4 groups with 8 rats in each group using a random number table control group ( group C), pulmonary arterial hypertension group ( group PAH), low-dose sildenafil group (group S1 ) and high-dose sildenafil group (group S2 ). The model of pul-monary arterial hypertension was established through combining left pneumonectomy with subcutaneous in-jection of 60 mg∕kg monocrotaline. Two percent sildenafil 30 and 50 mg∕kg were administered by intragastric gavage once a day for 3 consecutive weeks starting from 5 weeks after pneumonectomy in S1 and S2 groups, respectively. The chest was opened after the end of administration for measurement of mean pulmonary arte-rial pressure (mPAP) and right ventricular systolic pressure (RVSP). The hearts and lungs were excised for determination of the percentage of the thickness of tunica media of pulmonary arterioles, size of right ventricular cardiomyocytes, α-smooth muscle actin (α-SMA) expression (by immunohistochemistry) and expression of hypoxia-inducible factor-1α (HIF-1α) and HK-2 ( by Western blot). Results Compared with group C, the mPAP, RVSP and percentage of MT were significantly increased, the size of right ven-tricular cardiomyocytes was enlarged, and the expression of HIF-1α, HK-2 and α-SMA was up-regulated in PAH and S1 groups, and the RVSP and percentage of MT were significantly increased, the size of right ventricular cardiomyocytes was enlarged, and the expression of HIF-1α, HK-2 and α-SMA was up-regula-ted (P<0. 05), and no significant change was found in mPAP in group S2 (P>0. 05). Compared with group PAH, the percentage of MT was significantly decreased, the size of right ventricular cardiomyocytes was decreased, and the expression of HIF-1α, HK-2 and α-SMA was down-regulated in group S1 , and the mPAP, RVSP and percentage of MT were significantly decreased, the size of right ventricular cardiomyo-cytes was decreased, and the expression of HIF-1α, HK-2 and α-SMA was down-regulated in group S2 (P<0. 05). Conclusion The mechanism by which sildenafil inhibits proliferation of pulmonary vascular smooth muscle cells is related to inhibiting the expression of HK-2 in lung tissues in a rat model of pulmona-ry arterial hypertension.