PGF(2α) Causes Bronchoconstriction and Pulmonary Vasoconstriction Via Thromboxane Receptors in Rat Lung

We determined the vascular and airway effects of PGF(2α) and its mechanism of action on isolated-perfused lungs of rats were isolated and perfused at 50 ml/kg/min with Krebs-Henseleit bicarbonate buffer solution containing 3% bovine serum albumin. The lungs were ventilated with 21% O2 and 5% CO(2) at a tidal volume of 2 ml, frequency of 60 per minute and positive end expiratory pressure of 3 cmH(2)O. Following injection of 50 μg PGF(2α) into the afferent pulmonary catheter, there was a marked rise in pulmonary arterial pressure (Ppa) and in resistance to airflow across the lung (R(L)) and a fall in dynamic lung compliance (C(dyn)). Double vascular occlusion technique revealed that 29% of the rise in Ppa was due to an increase in upstream and 71% to downstream resistance. N(ω)-nitro-L-arginine. 100 μm, a NO synthase inhibitor potentiated the Ppa response two-fold with significant change in airway mechanics. Rat atrial natriuretic factor (r-ANF), 40 μg, quickly reversed the changes in Ppa, R(L) and C(dyn). Infusion of r-ANF prior to PGF(2α) attenuated the Ppa response by 38%, R(L) by 44% and C(dyn) by 12%. SQ 29548, a thromboxane receptor blocker and Cl, a protein kinase C (PKC) inhibitor, fully blocked both the vascular and airway responses to PGF(2α). PGF(2α) is a constrictor of pulmonary vessels and airways in rat lungs via thromboxane SQ 29548 receptors, thansduced by intracellular PKC.