Aim: 

In this study we tested the hypotesis that alteration in Aquaporin 2 expression/trafficking, in association with the polymorphism of a-adducin, may also contribute to the extracellular volume expansion observed in essential hypertension. To test this hypothesis in humans, we monitored the urinary AQP2 excretion. Moreover AQP2 expression/trafficking in a cellular model as well as in Milan hypertensive rats was evaluated.

Methods: 

Urinary excretion of AQP2 was quantitated by ELISA in hypertensive patients and in healthy subjects. Confocal microscopy, immunoblotting and biotynilation were used to evaluate AQP2 expression/trafficking in mutated adducin expressing renal cells (MCD4) and also in Milan hypertensive rat strain model of hypertension.

Result: 

AQP2 urinary excretion was significantly higher in hypertensive patients than in controls. Moreover in a subset of hypertensive patients carrying adducin mutation AQP2 excretion in response to acute sodium load was significantly higher compared to hypertensive patient carrying a normal adducin gene. In agreement with these results, expression of mutated adducin in MCD4 cells resulted in higher expression of AQP2 in the apical plasma membrane. Interestingly, cell surface expression of AQP2 was also higher in Milan hypertensive rat strain.

Conclusion: 

Toghether these results suggest that increase in AQP2 expression/trafficking possibly related to alteration of cytoskeleton structure, may contribute to the extracellular volume expansion observed in essential hypertension.