PGF2 alpha causes bronchoconstriction and pulmonary vasoconstriction via thromboxane receptors in rat lung

Abstract

We determined the vascular and airway effects of PGF2 alpha 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% CO2 at a tidal volume of 2 ml. frequency of 60 per minute and positive end expiratory pressure of 3 cmH2O. Following injection of 50 micrograms PGF2 alpha into the afferent pulmonary catheter, there was a marked rise in pulmonary arterial pressure (Ppa) and in resistance to airflow across the lung (RL) and a fall in dynamic lung compliance (Cdyn). 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 omega-nitro-L-arginine, 100 microns, a NO synthase inhibitor potentiated the Ppa response two-fold with significant change in airway mechanics. Rat atrial natriuretic factor (r-ANF), 40 micrograms quickly reversed the changes in Ppa, RL and Cdyn. Infusion of r-ANF prior to PGF2 alpha attenuated the Ppa response by 38%, RL by 44% and Cdyn 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 PGF2 alpha. PGF2 alpha is a constrictor of pulmonary vessels and airways in rat lungs via thromboxane SQ 29548 receptors, thansduced by intracellular PKC.

Fig. 1.

Change in longitudinal vascular segment pressure to a bolus dose of 50 μg PGF_2α. in 15 isolated-perfused rat lungs, measured by double occlusion. P_PA, pulmonary arterial pressure: P_mV, microvascular pressure: P_PA-P_mV, difference. Most of the pressure change was in the downstream segment.

Fig. 2.

Pulmonary arterial pressure response to PGF_2α without and with pre-treatment with atrial natriuretic factor(ANF). Values are means±SE of 6 experiments.

Fig. 3.

Pulmonary arterial pressure response to PGF_2α without and with pretreatment with N^w-nitro-L-arginine(NNLA). Values are means±SE of 12 experiments.