, 10:0

Spironolactone reduces aortic stiffness via blood pressure-dependent effects of canrenoate


  • Sonja B. Nikolic
    • Menzies Research Institute TasmaniaUniversity of Tasmania
  • Richard Wilson
    • Central Science LaboratoryUniversity of Tasmania
  • James L. Hare
    • Baker IDI Medical Research Institute
  • Murray J. Adams
    • School of Human Life Sciences, University of Tasmania
  • Lindsay M. Edwards
    • Centre of Human and Aerospace Physiological SciencesKing’s College London
    • Menzies Research Institute TasmaniaUniversity of Tasmania
Original Article

DOI: 10.1007/s11306-013-0557-2

Cite this article as:
Nikolic, S.B., Wilson, R., Hare, J.L. et al. Metabolomics (2014) 10: 0. doi:10.1007/s11306-013-0557-2


Spironolactone is thought to improve aortic stiffness via blood pressure (BP) independent (antifibrotic) effects, but the exact mechanism is unknown. We used metabolomics and hemodynamic measures to reveal the underlying actions of spironolactone in people with a hypertensive response to exercise (HRE). Baseline and follow-up serum samples from 115 participants randomized to 3 months spironolactone (25 mg/day) or placebo were analysed using liquid chromatography/mass spectrometry and nuclear magnetic resonance spectroscopy. Hemodynamic measures recorded at baseline and follow-up included aortic pulse wave velocity (stiffness) and 24 h ambulatory BP. Aortic stiffness was significantly reduced by spironolactone compared with placebo (−0.18 ± 0.17 vs 0.30 ± 0.16 m/s; p < 0.05), but this was no longer significant after adjustment for the change in daytime systolic BP (p = 0.132). Further, the change in aortic stiffness was correlated with the change in daytime and 24 h systolic BP (p < 0.05). Metabolomics detected 42 features that were candidate downstream metabolites of spironolactone (no endogenous metabolites), although none were correlated with changes in aortic stiffness (p > 0.05 for all). However, the spironolactone metabolite canrenoate was associated with the change in daytime systolic BP (r = −0.355, p = 0.017) and 24 h pulse pressure (r = −0.332, p = 0.026). This remained highly significant on multiple regression and was independent of age, body mass index and sex. Canrenoate appears to be an active metabolite with BP-dependent effects on the attenuation of aortic stiffness in people with HRE. This finding, together with the lack of change in endogenous metabolites, suggests that the antifibrotic effects of spironolactone could be BP-dependent.



Copyright information

© Springer Science+Business Media New York 2013