The effects of 17 alpha-methyltestosterone on myocardial function in vitro.
Testosterone analogs have been used as performance enhancers by athletes for more than 40 yr. We asked whether the anabolic steroid 17 alpha-methyl-4-androstene-17-ol-3-one (17 alpha-MT) would affect intrinsic contractile function of the heart. Male Sprague-Dawley rats, 125-150 g, were treated with 17 alpha-MT either parenterally or orally for up to 8 wk. Intrinsic contractile function of the hearts was assessed utilizing both the isolated working heart and isovolumic perfused heart preparations. Isolated working hearts from 17 alpha-MT-treated rats had a 45% decrease in heart work attributable largely to a similarly decreased stroke volume. Isovolumic perfused hearts from treated animals had elevated left ventricular systolic and diastolic pressures at similar interventricular volumes compared to controls. Rates of ventricular pressure development (+dP/dT) or relaxation (-dP/dT) were unchanged as a result of the treatment. However, static elastance was reduced in potassium-arrested hearts from the 17 alpha-MT treatment (63% increase in interventricular pressure), consistent with a limitation being imposed on stroke volume by a decreased myocardial compliance. Hydroxyproline content of the hearts was not altered by 17 alpha-MT treatment suggesting that increased stiffness was not a consequence of collagen proliferation. Treatment of the steroid rats with beta-aminopropionitrile, a compound that inhibits lysyl oxidase, restored the left ventricular volume-pressure relationship (elastance curve) to that of control hearts. Thus, chronic treatment with anabolic steroids appears to reduce left ventricular compliance, possibly related to an enhanced activity of lysyl oxidase, and results in increased crosslink formation between collagen strands in the extracellular matrix.
LeGros
T
T
Department of Physiology, Louisiana State University Health Sciences Center, School of Medicine, New Orleans, LA 70112, USA.
McConnell
D
D
Murry
T
T
Edavettal
M
M
Racey-Burns
L A
LA
Shepherd
R E
RE
Burns
A H
AH
D000284:Administration, Oral; D000629:Aminopropionitrile / Q000008:administration & dosage; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004343:Drug Implants; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006334:Heart Function Tests; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008777:Methyltestosterone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*; D009200:Myocardial Contraction / Q000187:drug effects* / Q000502:physiology; D010477:Perfusion; D008249:Protein-Lysine 6-Oxidase / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley
D004343:Drug Implants; D004791:Enzyme Inhibitors; D000629:Aminopropionitrile; D008249:Protein-Lysine 6-Oxidase; D008777:Methyltestosterone