Adrenomedullin (ADM) is a potent vasodilator peptide. To evaluate the effects of ADM on the ductus arteriosus (DA), we studied 16 near-term fetal sheep. We examined isolated rings of DA from 6 fetuses and measured isometric force generation to obtain concentration-response curves. ADM dilated the precontracted DA in a dose-dependent manner (ED50=3.5×10-8 M). This effect was not inhibited by Nw-nitro-L-arginine methyl ester. In 10 fetuses, we examined whether exogenous ADM inhibits closure of the DA after birth in vivo. Catheters were inserted into the main pulmonary artery and the ascending aorta to measure pressures, and into the superior vena cava (SVC) to administer drugs. An ultrasonic flow transducer was placed around the DA and the left pulmonary artery to measure flow continuously. Fetuses were delivered by cesarean section, two days after surgery, and were mechanically ventilated for 4 hours. In 5 fetuses, ADM was infused continuously into the SVC (0.18μg/kg*min) starting 45 min prior to delivery; 5 non-infused fetuses acted as controls. Hemodynamic variables were statistically compared between the two groups before and every 30 min after delivery. The mean pressure gradient from the ascending aorta to the pulmonary artery (mmHg), blood flow (ml/min*kg), and resistance (mmHg*min*kg/ml) across the DA in the ADM and control groups are shown in the table (*: p<0.05). At necropsy, in opposition to the controls, each DA was widely open in ADM group. These in-vitro and in-vivo data suggest that ADM has potent vasodilatory effects on the DA in fetal sheep and that this peptide can inhibit natural closure of the DA after birth.

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