Hyperpolarization or depolarization through movement of potassium(K+) across vascular smooth muscle cell membranes are known mechanisms involved in relaxation or contraction of pulmonary vessels. We have investigated the role of different K+ channels in isoproteronol (ISO) induced relaxation of isolated fourth generation pulmonary arteries (PA) and veins (PV) from preterm newborn lambs (122-123 d gestation, term 150 d). PA and PV rings were suspended in organ chambers filled with modified Krebs buffer (95% O2, 5% CO2, 37°C) and their isometric tension recorded. Contraction was induced with endothelin-1 for PA and U46619 for PV and relaxation induced with ISO (10-10 M to 10-4 M). Effect of ISO was then tested after pretreatment with different types of K+ channel blockers- glibenclamide (a blocker of ATPase-sensitive K+ channels [Katp], 4-aminopyridine (a blocker of voltage-dependent K+ channels [Kv]) and charybdotoxin (a blocker of calcium-activated K+ channels [Kca]). ISO induced greater relaxation in PV (65±5%) than in PA (13±4%) and this pattern was also observed in the presence of all the different K+ channel blockers. Glibenclamide did not affect ISO-induced relaxation in PA and PV. ISO-induced relaxation was decreased in PV treated with 4-aminopyridine (52±11%) and with charybdotoxin (56±1%) but was unchanged in PA. This suggests that Kv and Kca but not Katp are involved in ISO-induced relaxation in preterm ovine pulmonary veins.
