Potassium Channel Blockade Inhibits Shear Stress-Induced Pulmonary Vasodilation in the Ovine Fetus † 1752

Factors that contribute to the increase of pulmonary blood flow at birth include ventilation of the lung, increased O₂, and increased shear stress. Recent studies suggest that ventilation and O₂-induced pulmonary vasodilation are dependent upon the activation of potassium(K⁺) channels. To determine whether K⁺-channel activation mediates shear stress-induced pulmonary vasodilation in the fetus, we studied the effects of tetraethylammonium (TEA, a non-selective K⁺-channel blocker) and glibenclamide (Gli, an ATP-sensitive K⁺-channel blocker) on the pulmonary vascular response to partial compression of the ductus arteriosus (DA) in chronically prepared late-gestation fetal lambs (128-132 d of gestational age; term = 147 d). Catheters were inserted in the left pulmonary artery (LPA) for selective drug infusion, and in the main pulmonary artery (PAP), aorta (AoP), and left atrium (LAP) to measure pressure. An inflatable vascular occluder was placed around the DA. LPA flow (Qp) was measured with an ultrasonic flow transducer. After recovery from surgery (at least 2 d), the animals were randomly assigned to receive saline (6ml/h× 30 min; n=12), TEA (6ml/h = 1mg/min × 30min; n=5), or Gli (6ml/h= 1mg/min × 10 min; n=4) into the LPA during the DA compression (30min). Partial DA compression increased mean PAP in each group (15±2; 15±2; and 16±2 mmHg respectively). Qp increased in each group but was significantly lower in the TEA group than in the control group at 10, 20 and 30 min of the DA compression challenge (p<0.05). DA compression caused a time-related decrease in pulmonary vascular resistance (PVR) in the Gli and control groups but not in the TEA group (see table: * = p<0.05). We conclude that the shear stress response induced by DA compression during fetal life results from K⁺-channels activation. However, ATP-sensitive K⁺-channels are not involved in this phenomenon.

Table 1 No caption available.