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Departments of Medicine and Physiology, Cardiovascular Research Institute, University of California, San Francisco, California 94143-0521
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 (~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 (~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 (~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.
lung; pleura; water transport; aquaporin-1; pleural effusion
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