Loop diuretics activate the ‘classical’ circulating renin-angiotensin-aldosterone system (RAAS), increasing renin, angiotensin I and II (AngI; AngII), and aldosterone. Novel RAAS components include Ang1,7, Ang1,5 (counter-regulatory angiotensin metabolites) and AngIII and AngIV (AngII metabolites). We hypothesized that torsemide and furosemide, at equipotent dosages, would significantly and commensurately increase levels of these novel components, mirroring changes in the ‘classical’ RAAS.
Six, healthy, middle-aged, male beagles were randomized to receive torsemide (0.1mg/kg PO q12h), furosemide (2.0mg/kg PO q12h), or placebo for 10 days during 3 separate experiments in a cross-over design, each separated by a 10-day washout period. Blood was collected on days 1, 5, and 9 and 24-hour urine samples were collected, ending on days 2, 6, and 10. Serum aldosterone was quantified via liquid chromatography-mass spectrometry (LC-MS)/MS and angiotensin metabolites were quantified with LC-MS/MS and equilibrium analysis (Attoquant Diagnostics, Vienna Austria). Urine aldosterone was quantified via radioimmunoassay (Beckman Coulter) and used to calculate the urine aldosterone-to-creatinine ratio (UAldo:C). After repeated measures analysis and Bonferonni correction, variables with an adjusted P < 0.05 were investigated further, using Tukey’s method.
Serum AngI, AngII, Ang1,7, Ang1,5, AngIV, and aldosterone and the UAldo:C were significantly increased in the diuretic groups, as compared to placebo on days 5/6 and 9/10. Increases in these parameters were greatest in the torsemide group, but failed to reach significance. Serum AngIII increased after diuretic therapy, yet values did not differ significantly from placebo.
Novel components of the circulating RAAS are significantly increased during therapy with both torsemide and furosemide and mirror changes in the ‘classical’ RAAS.
Colorado State University
Marisa Ames, DVM, Diplomate ACVIM (cardiology) and assistant professor at Colorado State University College of Veterinary Medicine, is a 2007 graduate of the Ohio State University. She completed her cardiology residency and the Jane Lewis-Seaks postdoctoral fellowship at North Carolina State University. Her research interests include neurohormonal activation in heart failure (specifically the pharmacologic blockade of the renin-angiotensin-aldosterone system [RAAS], the effects various drugs on RAAS, and aldosterone breakthrough) and heartworm disease.
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