Effect of papaverine on pulmonary vascular permeability to proteins

Previous studies have suggested that papaverine, a drug commonly used in studies of transvascular fluid and solute exchange to eliminate confounding effects of changes in vascular tone, may itself increase vascular permeability. In this study, we determined the ability of papaverine to alter pulmonary vascular protein permeability by measuring the osmotic reflection coefficient (sigma) for total proteins in a canine isolated perfused left lower lung lobe (LLL) preparation. The reflection coefficient, determined by the hematocrit-protein double-indicator technique, for control LLL's was 0.83 +/- 0.04 (SE) (n = 7). In separate groups of LLL's, blood papaverine HCl concentrations of 10(-5), 10(-4), and 10(-3) M resulted in sigma's of 0.84 +/- 0.02 (n = 6), 0.73 +/- 0.04 (n = 7), and 0.53 +/- 0.04 (n = 6), respectively. When two LLL's from the 10(-4) M group with sigma's of 0.56 and 0.57 were excluded from the analysis, the average sigma for this group was 0.79 +/- 0.02. We conclude that papaverine increases protein permeability at a concentration of 10(-3) M but does so in only some lobes at 10(-4) M. These results suggest that caution be taken when using high concentrations of papaverine in fluid balance studies.