Role of aquaporin water channels in pleural fluid dynamics.
Continuous movement of fluid into and out of the pleural compartment occurs in normal chest physiology and in pathophysiological conditions associated with pleural effusions. RT-PCR screening and immunostaining revealed expression of water channel aquaporin-1 (AQP1) in microvascular endothelia near the visceral and parietal pleura and in mesothelial cells in visceral pleura. Comparative physiological measurements were done on wild-type vs. AQP1 null mice. Osmotically driven water transport was measured in anesthetized, mechanically ventilated mice from the kinetics of pleural fluid osmolality after instillation of 0.25 ml of hypertonic or hypotonic fluid into the pleural space. Osmotic equilibration of pleural fluid was rapid in wild-type mice (50% equilibration in <2 min) and remarkably slowed by greater than fourfold in AQP1 null mice. Small amounts of AQP3 transcript were also detected in pleura by RT-PCR, but osmotic water transport was not decreased in AQP3 null mice. In spontaneously breathing mice, the clearance of isosmolar saline instilled in the pleural space ( approximately 4 ml. kg(-1). h(-1)) was not affected by AQP1 deletion. In a fluid overload model produced by intraperitoneal saline administration and renal artery ligation, the accumulation of pleural fluid (approximately 0.035 ml/h) and was not affected by AQP1 deletion. Finally, in a thiourea toxicity model of acute endothelial injury causing pleural effusions and lung interstitial edema, pleural fluid accumulation in the first 3 h ( approximately 4 ml. kg(-1). h(-1)) was not affected by AQP1 deletion. These results indicate rapid osmotic equilibration across the pleural surface that is facilitated by AQP1 water channels. However, AQP1 does not appear to play a role in clinically relevant mechanisms of pleural fluid accumulation or clearance.
Song
Y
Y
Departments of Medicine and Physiology, Cardiovascular Research Institute, University of California, San Francisco, California 94143-0521, USA.
Yang
B
B
Matthay
M A
MA
Ma
T
T
Verkman
A S
AS
D000818:Animals; D051398:Aquaporin 1; D051399:Aquaporin 2; D051400:Aquaporin 3; D051401:Aquaporin 4; D051402:Aquaporin 5; D051403:Aquaporin 6; D020346:Aquaporins / Q000032:analysis / Q000235:genetics* / Q000378:metabolism*; D001692:Biological Transport / Q000502:physiology; D015870:Gene Expression / Q000502:physiology; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins; D051379:Mice; D018345:Mice, Knockout; D010994:Pleura / Q000737:chemistry / Q000378:metabolism*; D010996:Pleural Effusion / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014867:Water / Q000378:metabolism
C496021:Aqp1 protein, mouse; C496024:Aqp2 protein, mouse; C496028:Aqp3 protein, mouse; C496031:Aqp4 protein, mouse; C496038:Aqp5 protein, mouse; C496042:Aqp6 protein, mouse; C491927:Aqp7 protein, mouse; C491638:Aqp9 protein, mouse; D051399:Aquaporin 2; D051401:Aquaporin 4; D051402:Aquaporin 5; D051403:Aquaporin 6; D020346:Aquaporins; D007473:Ion Channels; D008565:Membrane Proteins; D012333:RNA, Messenger; C108330:aquaporin 8; D014867:Water; D051398:Aquaporin 1; D051400:Aquaporin 3