The involvement of K+ATP channels in the regulation of pulmonary and systemic vascular tone in the pig

We evaluated the involvement of K+ATP channels in the regulation of pulmonary and systemic vascular tone in anaesthetised, mechanically ventilated, indomethacin-treated pigs. The animals were divided into three groups of six pigs. To induce opening of K+ATP channels, to the first group we gave cromakalim as a bolus of 80 mu-m/ml, i.v. followed by drop by drop infusion of 1 mu-g/kg/min for 120 min. To the second group, 120 min after the start of cromakalim infusion, we gave glibenclamide, a sulfonylurea compound, at a dose of 10 mg/kg over 5 min, to block K +ATP channels activity. The third group was treated with glibenclamide only at the same dose of group two. Cromakalim decreased systemic arterial pressure, without any significant effect on pulmonary arterial pressure. In group two, when glibenclamide was administered, pulmonary arterial pressure markedly increased, while systemic arterial pressure returned to control value. Glibenclamide given alone not after cromakalim caused both systemic and pulmonary arterial pressure to rise, with the greater effect on the pulmonary system. These results indicate that K+ATP channels are involved in the maintenance of a low pulmonary vascular tone and represent a very effective mechanism of eliciting vasodilatation and reducing a hypertensive state in the systemic vascular bed.