Abnormal increase in urinary aquaporin-2 excretion in response to hypertonic saline in essential hypertension

Abstract

Background: Dysregulation of the expression/shuttling of the aquaporin-2 water channel (AQP2) and the epithelial sodium channel (ENaC) in renal collecting duct principal cells has been found in animal models of hypertension. We tested whether a similar dysregulation exists in essential hypertension. Methods. We measured urinary excretion of AQP2 and ENaC -subunit corrected for creatinine (u-AQP2CR, u-ENaC-CR), prostaglandin E2 (u-PGE2) and cyclic AMP (u-cAMP), fractional sodium excretion (FENa), free water clearance (CH2O), as well as plasma concentrations of vasopressin (AVP), renin (PRC), angiotensin II (Ang II), aldosterone (Aldo), and atrial and brain natriuretic peptide (ANP, BNP) in 21 patients with essential hypertension and 20 normotensive controls during 24-h urine collection (baseline), and after hypertonic saline infusion on a 4-day high sodium (HS) diet (300 mmol sodium/day) and a 4-day low sodium (LS) diet (30 mmol sodium/day). Results: At baseline, no differences in u-AQP2CRor u-ENaC-CRwere measured between patients and controls. U-AQP2 CRincreased significantly more after saline in patients than controls, whereas u-ENaC-CRincreased similarly. The saline caused exaggerated natriuretic increases in patients during HS intake. Neither baseline levels of u-PGE2, u-cAMP, AVP, PRC, Ang II, Aldo, ANP, and BNP nor changes after saline could explain the abnormal u-AQP2CRresponse. Conclusions: No differences were found in u-AQP2CRand u-ENaC -CRbetween patients and controls at baseline. However, in response to saline, u-AQP2CRwas abnormally increased in patients, whereas the u-ENaC-CRresponse was normal. The mechanism behind the abnormal AQP2 regulation is not clarified, but it does not seem to be AVP-dependent. Clinicaltrial.gov identifier. NCT00345124. © 2012 Graffe et al; licensee BioMed Central Ltd.