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BAS/BSCR poster abstract
BAS/BSCR24 Spironolactone reverses the adverse effects of aldosterone and hypoxia on adipose tissue
  1. S Withers,
  2. C Agabiti-Rosei,
  3. D M Livingstone,
  4. R Aslam,
  5. R A Malik,
  6. A M Heagerty
  1. Cardiovascular Research Group, School of Biomedicine, University of Manchester, Manchester, UK

Abstract

We tested the hypothesis that aldosterone causes a loss of the normal anticontractile function of healthy fat via a hypoxia-related pathway, which can be rescued using spironolactone. Healthy rat mesenteric arteries (∼250%μM diameter) and perivascular fat were investigated using wire myography and Perl's Prussian blue staining for activated macrophages. The effects of aldosterone%±spironolactone were assessed after incubation for 10 min and 3 h, and experimental hypoxia (95% N2/5% CO2) for 2.5 h. Contractile responses were calculated as a percentage of KCl contraction and expressed as mean±SEM. Macrophage activation was expressed semiquantitatively and expressed as macrophage abundance values (MAV). The anticontractile capacity of healthy fat was lost upon incubation with aldosterone (5 nM) (fat: 90±4% n=36, fat+10 min aldosterone: 165±5% n=25, fat+3 h aldosterone 172%±12% n=7) and was associated with an increase in activated macrophages (immediately fixed: 2.2±0.5% n=5 vs 10 min aldosterone: 3.8±0.4% n=5, p=NS; immediately fixed: 2.2±0.5% n=5 vs 3 h aldosterone: 4.7±0.3% n=5, p=0.0313). Spironolactone (10%μM) restored anticontractile activity after incubation for 3 h only (3 h:111±4% p<0.05, n=5) and caused a significant reduction in macrophage activation (3.0±1.0%, n=5). As for aldosterone, hypoxia caused an increase in contractility (149±17% n=15) and macrophage activation (5.5±0.5% n=5), which was reversed upon incubation with spironolactone (contractility: 120±12% n=5;MAV: 3.3±0.8%, n=3, p=0.500). Aldosterone ameliorates the anticontractile capacity of healthy fat by a common pathway to hypoxia, which correlates with an increase in the number of activated macrophages within adipose tissue. Spironolactone can restore the effect of hypoxia on contractility and macrophage activation in the absence of aldosterone.

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