title: Hypoxia modulates rapid effects of aldosterone on oxidative metabolism in human calf muscle.
abstract: Non-genomic effects of aldosterone on oxidative metabolism of skeletal muscle have been shown, recently. To further characterize these rapid effects on the increase of phosphocreatine (PCr) in the recovery period after isometric exercise, a randomized cross-over placebo-controlled study was conducted on 9 healthy volunteers. Hypoxia was chosen to test the dependence of the effect on oxygen supply and thus its relation to oxidative vs non-oxidative metabolism. Parameters related to the energy metabolism of calf muscles were measured by 31P magnetic resonance spectroscopy during four repetitive contractions in four different tests (hypoxia [FiO2=0.13] vs normoxia [FiO2=0.21], +/- 0.5 mg aldosterone). The area-under-curves of post-exercise PCr levels after the 4th contraction were significantly increased by aldosterone vs placebo during normoxia (875.5 +/- 5.1 vs 857.2 +/- 8.3%-min; p=0.02). In addition, aldosterone induced an undershoot of inorganic phosphate (Pi) in the recovery after isometric exercise (77.5 +/- 5.4 vs 88.9 +/- 5.1 mmol/l x min; p=0.05). Hypoxia blocked effects of aldosterone on PCr overshoot and Pi undershoot. Concentrations of ATP, ADP, phosphomonoesters, and intracellular pH were not affected by those interventions. In conclusion, these data demonstrate rapid actions of aldosterone on post-excercise PCr and Pi levels in human calf muscle, which are blocked by hypoxia. We hypothesize that aldosterone rapidly interferes with oxidative metabolism probably by direct modulation of ATP-turnover, which is induced by an oxygen-dependent imbalance of the ATP-synthesis and utilization rate.
authors.affiliation: Institute of Clinical Pharmacology, Klinikum Mannheim, University of Heidelberg, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Christ
authors.forename: J
authors.initials: J
authors.lastname: Zange
authors.forename: C P
authors.initials: CP
authors.lastname: Janson
authors.forename: K
authors.initials: K
authors.lastname: Müller
authors.forename: P
authors.initials: P
authors.lastname: Kuklinski
authors.forename: B M
authors.initials: BM
authors.lastname: Schmidt
authors.forename: H C
authors.initials: HC
authors.lastname: Tillmann
authors.forename: R
authors.initials: R
authors.lastname: Gerzer
authors.forename: M
authors.initials: M
authors.lastname: Wehling
mesh_terms: D000328:Adult; D000332:Aerobiosis; D000450:Aldosterone / Q000494:pharmacology*; D000693:Anaerobiosis; D018592:Cross-Over Studies; D005260:Female; D006439:Hemodynamics; D006728:Hormones / Q000097:blood; D006801:Humans; D000860:Hypoxia / Q000503:physiopathology*; D007537:Isometric Contraction; D007866:Leg; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000502:physiology; D010084:Oxidation-Reduction / Q000187:drug effects; D013997:Time Factors
chemical_list: D006728:Hormones; D000450:Aldosterone