Aim: In this study we tested the hypothesis that alteration in Aquaporin 2 (AQP2) expression/trafficking may contribute to the extracellular volume expansion observed in hypertension. Methods: To test this hypothesis we monitored the urinary AQP2 excretion in patients with essential hypertension carrying polymorphisms of the cytoskeletal protein adducin (ADD) known for increasing tubular sodium reabsorption. AQP2 urinary excretion was also measured in Milan Hypertensive Strain (MHS) rats carrying single nucleotide polymorphisms (SNPs) of ADD genes. AQP2 trafficking to the apical plasma membrane was also evaluated in MCD4 cells upon overexpression of human SNPs of ADD1 gene. Results: AQP2 excretion was significantly higher in hypertensive patients than in controls. In addition, after two hours of acute sodium load, AQP2 excretion was significantly higher in patients carrying ADD mutation. MHS rats showed a significant increase in total AQP2 protein and an increased expression at the apical plasma membrane compared to normotensive rats. In MCD4 cells, AQP2 trafficking to the apical plasma membrane was significantly increased upon co-expression of mutated ADD. Conclusions: Taken together, these observations suggest that increase in AQP2 expression/trafficking possibly related to alteration of cytoskeleton structure, may contribute to the extracellular volume expansion observed in hypertension.
Aquaporin 2 and Adducin Polymorphism Impact on Essential Hypertension
PROCINO, Giuseppe;TAMMA, GRAZIA;
2008-01-01
Abstract
Aim: In this study we tested the hypothesis that alteration in Aquaporin 2 (AQP2) expression/trafficking may contribute to the extracellular volume expansion observed in hypertension. Methods: To test this hypothesis we monitored the urinary AQP2 excretion in patients with essential hypertension carrying polymorphisms of the cytoskeletal protein adducin (ADD) known for increasing tubular sodium reabsorption. AQP2 urinary excretion was also measured in Milan Hypertensive Strain (MHS) rats carrying single nucleotide polymorphisms (SNPs) of ADD genes. AQP2 trafficking to the apical plasma membrane was also evaluated in MCD4 cells upon overexpression of human SNPs of ADD1 gene. Results: AQP2 excretion was significantly higher in hypertensive patients than in controls. In addition, after two hours of acute sodium load, AQP2 excretion was significantly higher in patients carrying ADD mutation. MHS rats showed a significant increase in total AQP2 protein and an increased expression at the apical plasma membrane compared to normotensive rats. In MCD4 cells, AQP2 trafficking to the apical plasma membrane was significantly increased upon co-expression of mutated ADD. Conclusions: Taken together, these observations suggest that increase in AQP2 expression/trafficking possibly related to alteration of cytoskeleton structure, may contribute to the extracellular volume expansion observed in hypertension.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
