Increased urinary aquaporin‐2 excretion in response to furosemide in patients with chronic heart failure

Abstract

Objective. Patients with chronic heart failure (CHF) have decreased ability to excrete water and increased urinary excretion of aquaporin‐2 (U‐AQP2). The natriuretic and diuretic effects of furosemide are antagonized by an increased reabsorption of sodium and water in the collecting ducts. It is unknown whether aquaporin‐2 (AQP2) renal water channels are involved in this compensatory reabsorption. We tested the hypothesis that U‐AQP2 increases after a single intravenous dose of furosemide in CHF patients. Material and methods. In a randomized, single‐blind, placebo‐controlled, crossover study, we measured the effect of furosemide (80 mg) on U‐AQP2, urine volume, free water clearance (C_H2O) and fractional excretion of sodium (FE_Na) in 12 CHF patients. Plasma concentrations of vasopressin (AVP), renin (PRC), angiotensin II (Ang II), aldosterone (Aldo), atrial (ANP) and brain natriuretic peptides (BNP) were measured during the study. U‐AQP2 and hormones were determined by radioimmunoassays. Results. Furosemide increased U‐AQP2 (140 %), urine volume (280 %), C_H2O (95 %) and FE_Na by a factor of 15 (p<0.008 for all), and also AVP (51 %), PRC, Ang II (86 %) and Aldo (59 %) (p<0.021 for all). ANP and BNP did not change. Conclusions. In CHF, furosemide increased the vasopressin level, which stimulated water reabsorption via the APQ2 water channels. This is most likely a compensatory phenomenon in addition to the increase in the renin‐angiotensin system to prevent excess loss of sodium and water. However, both these effects were overridden by the effect of furosemide, as shown by increased free water clearance and sodium excretion.

• Arginine vasopressin
• clinical trial
• loop diuretics
• water channels

Acknowledgements

Laboratory technicians Lisbeth Mikkelsen, Anne Jaritz‐Nielsen, Eva Mølgaard Jensen, Susan Milton Rasmussen, Henriette Hedelund Vorup Simonsen and Anne Mette Ravn Torstensen are thanked for skilful technical assistance and commitment. Nurses Helle Haubjerg and Sanne Thomsen are thanked for performing the echocardiographies and for helping with recruitment of the patients. The study was supported by grants from Ringkøbing County and the experiments complied with the current laws of Denmark inclusive of ethics approval.