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 expre ssion of water channel aquaporin-1 (AQP1) in microvascular endothelia near the visceral and parietal pleura and in mesothelial cells in visceral pleur a. Comparative physiological measurements were done on wildtype vs. AQP1 nu ll mice. Osmotically driven water transport was measured in anesthetized, m echanically ventilated mice from the kinetics of pleural fluid osmolality a fter instillation of 0.25 ml of hypertonic or hypotonic fluid into the pleu ral space. Osmotic equilibration of pleural fluid was rapid in wild-type mi ce (50% equilibration in <2 min) and remarkably slowed by greater than four fold 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 sal ine instilled in the pleural space (<similar to>4 ml.kg(-1).h(-1)) was not affected by AQP1 deletion. In a fluid overload model produced by intraperit oneal saline administration and renal artery ligation, the accumulation of pleural fluid (similar to0.035 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 i n the first 3 h (similar to4 ml.kg(-1).h(-1)) was not affected by AQP1 dele tion. 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 a ccumulation or clearance.