Pentoxifylline relaxes isolated pulmonary arteries after preconstriction with norepinephrine

Abstract

Pentoxifylline (PTX) is a methylxanthine derivative which improves systemic microvascular flow and tissue oxygen delivery, presumably through actions on platelet aggregation and erythrocyte deformability. Although PTX also improves pulmonary vascular flow, recent evidence suggests that part of this improvement may be due to pulmonary vasodilation. To evaluate these effects we studied isolated rabbit lobar pulmonary artery (PA) ring segments to determine if PTX had direct effects on PA tissues and whether these effects could be modulated pharmacologically or by endothelial disruption. PTX had no effect on PA at resting tension. However, if the PA tension was actively increased by norepinephrine (5 microM), subsequent PTX application caused concentration-dependent PA relaxation. Relaxation occurred promptly and was maximal within 45-60 s. The threshold PTX concentration necessary for relaxation was 1 microM. PTX-induced relaxation was not affected by pretreatment with the cyclo-oxygenase inhibitor indomethacin (1 microM). Endothelial disruption by gentle rubbing of the intimal PA surface abolished relaxation of preconstricted PA by acetylcholine, but had no effect on relaxation by PTX. Although PA at resting tension displayed no response to PTX, PA constriction by norepinephrine in the presence of PTX concentrations greater than 10 microM was significantly decreased. These data indicate that PTX has direct actions on isolated rabbit PA which are not blocked by indomethacin nor require the presence of intact endothelium. Furthermore, PTX can suppress norepinephrine-induced constriction of isolated PA.