Abnormal increase in urinary aquaporin-2 excretion in response to hypertonic saline in essential hypertension
1 Department of Medical Research, Holstebro Hospital, Laegaardvej 12, 7500 Holstebro, Denmark
2 Department of Medicine, Holstebro Hospital, Holstebro, Denmark
3 University of Aarhus, Aarhus, Denmark
BMC Nephrology 2012, 13:15 doi:10.1186/1471-2369-13-15Published: 27 March 2012
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.
We measured urinary excretion of AQP2 and ENaC β-subunit corrected for creatinine (u-AQP2CR, u-ENaCβ-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).
At baseline, no differences in u-AQP2CR or u-ENaCβ-CR were measured between patients and controls. U-AQP2CR increased significantly more after saline in patients than controls, whereas u-ENaCβ-CR increased 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-AQP2CR response.
No differences were found in u-AQP2CR and u-ENaCβ-CR between patients and controls at baseline. However, in response to saline, u-AQP2CR was abnormally increased in patients, whereas the u-ENaCβ-CR response was normal. The mechanism behind the abnormal AQP2 regulation is not clarified, but it does not seem to be AVP-dependent.