HEPES BUFFER PERFUSATE ALTERS RABBIT LUNG ENDOTHELIAL PERMEABILITY

N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES) has been s hown to cause changes in cultured endothelial cells and smooth muscle function at concentrations from 5 to 25 mM. To determine whether HEPES also affects vascular permeability, the effects of two buffers, HEPES and phosphate, were compared in isolated perfused rabbit lungs. Hemod ynamic parameters and vascular protein permeability-surface area produ cts (PS) were measured after perfusion with the buffers. Endothelial p ermeability was measured for an anionic and a cationic albumin to asse ss the charge effects of the zwitterion buffer. With HEPES, there were no changes in vascular pressure or resistance but permeability was af fected. Cationic albumin permeability increased with 12 mM HEPES (8.7p hosphate --> 30(12 mM HEPES) X MI . min-1 . g dry lung-1 X 10(-2)) as did the anionic albumin PS (2.7phosphate --> 3,52(12 mM HEPES)). The c ationic PS returned to baseline (8.1(60 mm HEPES)) at 60 mM HEPES, but the anionic PS did not change from the 12 mM HEPES (4.01(60 mm HEpEs) ). In summary, we find that HEPES is not innocuous. Although hemodynam ic parameters did not change, endothelial permeability was increased w hen HEPES was used at normal concentrations. Therefore, HEPES should b e used with caution as a physiological buffer in perfused organ system s.