Effects of cardiogenic edema fluid on ion and fluid transport in the adult lung

1 Canadian Institutes of Health Research Group in Lung Development and 2 Physiology and Experimental Medicine, 3 Genetics and Genome Biology of the Research Institute of the Hospital for Sick Children, and Departments of 4 Paediatrics, 5 Physiology, and 6 Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada; and Departments of 7 Physiology and 8 Pediatrics, Emory University, Atlanta, Georgia Submitted 29 November 2006 ; accepted in final form 1 June 2007 We have previously shown that cardiogenic pulmonary edema fluid (EF) increases Na + and fluid transport by fetal distal lung epithelia (FDLE) (Rafii B, Gillie DJ, Sulowski C, Hannam V, Cheung T, Otulakowski G, Barker PM and O'Brodovich H. J Physiol 544: 537–548, 2002). We now report the effect of EF on Na + and fluid transport by the adult lung. We first studied primary cultures of adult type II (ATII) epithelium and found that overnight exposure to EF increased Na + transport, and this effect was mainly due to factors other than catecholamines. Plasma did not stimulate Na + transport in ATII. Purification of EF demonstrated that at least some agent(s) responsible for the amiloride-insensitive component resided within the globulin fraction. ATII exposed to globulins demonstrated a conversion of amiloride-sensitive short-circuit current ( I sc ) to amiloride-insensitive I sc with no increase in total I sc . Patch-clamp studies showed that ATII exposed to EF for 18 h had increased the number of highly selective Na + channels in their apical membrane. In situ acute exposure to EF increased the open probability of Na + -permeant ion channels in ATII within rat lung slices. EF did increase, by amiloride-sensitive pathways, the alveolar fluid clearance from the lungs of adult rats. We conclude that cardiogenic EF increases Na + transport by adult lung epithelia in primary cell culture, in situ and in vivo. pulmonary edema fluid; alveolar type ii epithelium; sodium channels; lung fluid clearance Address for reprint requests and other correspondence: H. O'Brodovich, Depts. of Paediatrics and Physiology, Univ. of Toronto, Hospital for Sick Children, 555 Univ. Ave., Toronto, Ontario, Canada M5G-1X8 (e-mail: hugh.obrodovich{at}sickkids.ca )