Effect of pentoxifylline in rabbit pulmonary circulation: influence of age and vasomotor tone

Abstract

We determined the influence of vasomotor tone and age on pentoxifylline (PTX) effects in rabbit lungs. Lungs of adult, juvenile, and neonatal rabbits were isolated and perfused with blood at constant flow in zone 3. In adult lungs only, pressures were measured in 20- to 50-microns-diameter subpleural arterioles and venules (by micropuncture) to partition the circulation into arteries, microvessels, and veins during baseline, after PTX infusion (20 mg/kg), and terminally, after treatment with papaverine. In some adult and juvenile lungs, vasomotor tone was elevated with KCl, and some adult lungs were pretreated with indomethacin to inhibit cyclooxygenase. We found that PTX's vasodilator effect was influenced by age; it was approximately 52, approximately 65, and approximately 82% as effective as papaverine in untreated neonatal, juvenile, and adult lungs, respectively, and approximately 49 and approximately 93% as effective as papaverine in KCl-constricted adult and juvenile lungs, respectively. The site(s) of PTX action depended on basal vasomotor tone; in lungs with moderate tone, PTX dilated arteries only, and in lungs with high tone, PTX dilated both arteries and veins. Cyclooxygenase inhibition did not attenuate PTX effects. We conclude that, in rabbit lungs, PTX dilates arteries and veins and that the magnitude of PTX effect is dependent on age and basal vasomotor tone.