Abstract:
Objective To investigate the effect of tadalafil on endothelial function of femoral artery in rat model of preeclampsia. Methods Thirty-two female Sprague-Dawley(SD) rats aged 6-8 weeks were randomly divided into control group, N-nitro-L-arginine-methyl-ester(l-NAME) model group(l-NAME group), l-NAME+low-dose tadalafil group(LT group) and l-NAME+high-dose tadalafil group(HT group), with 8 rats in each group. The blood pressure of the pregnant rats was measured on day 0, 5, 10, 15 and 20 of pregnancy, and the 24 h urine protein was measured on day 0 and 18 of pregnancy. On the 19 th day of pregnancy, the small animal ultrasound was used to detect and calculate the femoral artery blood flow-mediated dilatation(FMD) and wall shear stress(WSS) of the pregnant rats. Rats were sacrificed on the 20 th day of pregnancy, body length and weight of fetuses were measured. Soluble vascular endothelial growth factor receptor 1(sFlt-1), placental growth factor(PlGF), nitric oxide(NO) and endothelial nitric oxide synthase(eNOS) levels in plasma were detected and the sFlt-1/PlGF ratio was calculated. Results Tadalafil improved l-NAME-induced gestational hypertension: the systolic, diastolic and mean arterial pressures in the l-NAME group were significantly higher than those in the other groups(P<0.05). On the 18 th day of pregnancy, compared with baseline, the urine protein of l-NAME group was significantly increased, and the increase was significantly higher in l-NAME group than that in control, LT and HT groups(55.44±21.81)vs(9.22±11.79),(27.69±15.47),(17.80±11.99)mg/24 h, all P<0.05. In the control, LT and HT groups, the FMD of the pregnant rats reached the peak at 120 s, and in the l-NAME group, it reached the peak at 240 s. The peak levels of FMD in the control (14.99±1.11)% and HT groups (13.69±1.60)% were higher than those in the LT (11.81±1.57)% and l-NAME groups (5.62±1.04)%, and which in the LT group was higher than that in the l-NAME group(P<0.05). The WSS of the 4 groups of pregnant rats decreased with time, and the WSS of the l-NAME group was higher than other groups(P<0.05). The weight gain during pregnancy, the length and weight of the fetuses in l-NAME group were significantly lower than those of the other groups(P<0.05). The sFlt-1 and sFlt-1/PlGF in plasma of the l-NAME group were significantly higher than those in the other groups. The PlGF in plasma of the l-NAME group was lower than that in the control group and the HT group, and the plasma NO level was lower than the other groups(P<0.05). Plasma eNOS in the control group was significantly higher than that in the l-NAME group(P<0.05). Conclusion Prophylactic administration of tadalafil can improve hypertension, proteinuria and fetal growth restriction induced by l-NAME in pregnant rats, regulate the balance of vascular growth factors and protect vascular endothelial function, suggesting that tadalafil may have potential value in the prevention of preeclampsia.