INCREASED URINARY EXCRETION OF AQUAPORIN 2 IN PATIENTS WITH ESSENTIAL HYPERTENSION: GENETIC ASSOCIATION WITH POLYMORPHISM OF THE CYTOSKELE- TAL PROTEIN ALPHA-ADDUCIN

Essential hypertension refers to a lasting increase in blood pressure with heterogeneous genetic and environmental causes. In developed countries, essential hypertension affects 25-35% of the adult population. Several studies indicate that the pathophysiology of essential hypertension depends on the primary or secondary inability of the kidney to excrete sodium at a normal blood pressure. In this study we tested the hypothesis that alteration in Aquaporin 2 (AQP2) expression/trafficking may also contribute to the extracellular volume expansion observed in hypertension. To test this hypotesis in humans, we monitored the urinary AQP2 excretion as biomarker of kidney concen- trating ability. Patients with essential hypertension were examined to determine if urinary excretion of AQP2 differed from that of healthy control subjects. Urinary excretion of AQP2 was measured in hyper- tensive patients without medication and in 13 healthy subjects. AQP2 excretion, quantitated by ELISA, was significantly higher in hypertensive patients than in controls (3264±143 vs 1659±191 fmol/mg creatinine; p<0.002). Since abnormalities of tubular sodium reabsorption observed in essential hypertension were previously be shown to be associated with the polymorphism of the cytoskeletal protein alpha-adducin, in a subset of hypertensive pa- tients AQP2 excretion was examined after acute sodium load (2 L of saline (Na+ 310 mEq) infused i.v.) and the genetic association with polymorphism of alpha-adducin was evaluated. Prelimi- nary results suggest that, after two hours of acute sodium load, AQP2 excretion was significantly higher (3216±277 (n=8) vs 2669±277 n=22 fmol/mg creatinine; P<0.01) in patients carrying ad- ducin mutation with respect to hypertensive patient carrying a normal adducin gene. Conclusions: Urinary AQP2 excretion was increased in hypertensive patients. Moreover, higher urinary AQP2 excretion after acute sodium load positively associated with adducin mutation. This suggests that increase in AQP2 expression/trafficking possibly related to alteration of cytoskeleton structure, may contribute to the extracellular volume expansion observed in hypertension.