Increased Expression of AQP 1 and AQP 5 in Rat Lungs Ventilated with Low Tidal Volume is Time Dependent

Abstract

Background and GoalsMechanical ventilation (MV) can induce or worsen pulmonary oedema. Aquaporins (AQPs) facilitate the selective and rapid bi-directional movement of water. Their role in the development and resolution of pulmonary oedema is controversial. Our objectives are to determine if prolonged MV causes lung oedema and changes in the expression of AQP 1 and AQP 5 in rats.Methods25 male Wistar rats were subjected to MV with a tidal volume of 10 ml/kg, during 2 hours (n = 12) and 4 hours (n = 13). Degree of oedema was compared with a group of non-ventilated rats (n = 5). The expression of AQP 1 and AQP 5 were determined by western immunoblotting, measuring the amount of mRNA (previously amplified by RT-PCR) and immunohistochemical staining of AQPs 1 and 5 in lung samples from all groups.ResultsLung oedema and alveolar-capillary membrane permeability did not change during MV. AQP-5 steady state levels in the western blot were increased (p<0.01) at 2 h and 4 h of MV. But in AQP-1 expression these differences were not found. However, the amount of mRNA for AQP-1 was increased at 2 h and 4 h of MV; and for AQP 5 at 4 h of MV. These findings were corroborated by representative immunohistochemical lung samples.ConclusionIn lungs from rats ventilated with a low tidal volume the expression of AQP 5 increases gradually with MV duration, but does not cause pulmonary oedema or changes in lung permeability. AQPs may have a protective effect against the oedema induced by MV.

Expression of aquaporins 1 and 5 in a model of ventilator‐induced lung injury and its relation to tidal volume

“…The causal mechanism of VILI appears to be pulmonary distension rather than the increase of pressure itself, as shown by a number of studies in animals (Dreyfuss & Saumon, 1998). Similar results were also found in a previous study conducted by our group, in which mechanical ventilation at harmless tidal volumes sustained for 4 h resulted in no significant increase of pulmonary permeability, even though there seem to be a trend (Fabregat et al 2014). Although, in our study, we did not measure cardiac output in the ventilated animals or parameters such as pulmonary arterial pressure, changes of which can be involved in the onset of pulmonary oedema, quantification of microvascular permeability using Evans Blue dye correlated well with the leak of labelled albumin into the skin and the airway of rodents (Rogers et al 1989).…”

“…In accord with this, Hegeman et al (2013) observed an increase of pulmonary permeability in a model of prolonged pulmonary ventilation with low tidal volumes (7 ml kg −1 ) in mice; however, as in our experiment, statistical significance was not reached in spite of a trend of values. Similar results were also found in a previous study conducted by our group, in which mechanical ventilation at harmless tidal volumes sustained for 4 h resulted in no significant increase of pulmonary permeability, even though there seem to be a trend (Fabregat et al 2014). Further studies will be necessary to confirm or refute these results.…”

“…In light of the present results, together with those previously obtained by our group (Fabregat et al 2014) in which the duration of mechanical ventilation was varied, it appears that MV increases the expression of AQP1 and AQP5 mRNA even though the final protein expression varies in the specific scenarios created in our experiments. The AQP1 protein expression would decrease in the presence of lung injury and AQP5 protein expression would increase when MV causes no lung injury, as reflected by an increase in the pulmonary wet weight to dry weight ratio (Fabregat et al 2014).…”

Dexamethasone attenuates methacholine‐mediated aquaporin 5 downregulation in human nasal epithelial cells via suppression of NF‐κB activation

“…In animal models induced by lipopolysaccharide or adenovirus, AQP5 expression is decreased in lung inflammation or lung injury . In addition, AQP5 has a protective effect against the edema induced by mechanical ventilation . On the other hand, several studies have shown that AQP5 contributes to the formation of edema in rat lung.…”

Differential Expression of Aquaporins in Experimental Models of Acute Lung Injury

“…The main conclusion so far has been that, despite differences in expression in the various studies, AQP1 and AQP5 provide the principal route for osmotically driven water transport between airspace and capillary compartments (20)(21)(22)(23)(24)(25)(26)(27). However, Song et al used mice deficient in AQP1, AQP4 and AQP5 to test the hypothesis that aquaporins are important in neonatal lung fluid balance, adult lung fluid clearance and formation of lung oedema after acute lung injury (24).…”