eCite Digital Repository

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

Citation

Nikolic, SB and Wilson, R and Hare, JL and Adams, MJ and Edwards, LM and Sharman, JE, Spironolactone reduces aortic stiffness via blood pressure-dependent effects of canrenoate, Metabolomics, 10, (1) pp. 105-113. ISSN 1573-3882 (2014) [Refereed Article]

Copyright Statement

Copyright 2013 Springer Science+Business Media

DOI: doi:10.1007/s11306-013-0557-2

Abstract

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.

Item Details

Item Type:Refereed Article
Keywords:Metabolomics,  Canrenone,  Canrenoate, Hypertension , Exercise
Research Division:Medical and Health Sciences
Research Group:Cardiorespiratory Medicine and Haematology
Research Field:Cardiology (incl. Cardiovascular Diseases)
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Cardiovascular System and Diseases
Author:Nikolic, SB (Mrs Sonja Nikolic)
Author:Wilson, R (Dr Richard Wilson)
Author:Adams, MJ (Dr Murray Adams)
Author:Sharman, JE (Professor James Sharman)
ID Code:85356
Year Published:2014
Web of Science® Times Cited:5
Deposited By:Menzies Institute for Medical Research
Deposited On:2013-07-02
Last Modified:2017-11-01
Downloads:0

Repository Staff Only: item control page