Epiandrosterone, a metabolite of testosterone precursor, blocks L-type calcium channels of ventricular myocytes and inhibits myocardial contractility

J Mol Cell Cardiol. 2002 Jun;34(6):679-88. doi: 10.1006/jmcc.2002.2008.


The dehydroepiandrosterone metabolite epiandrosterone (EPI) inhibits the pentose phosphate pathway (PPP) and dilates isolated blood vessels pre-contracted by partial depolarization. We found that EPI (10-100 microM) also dose-dependently decreases left-ventricular developed pressure (LVDP), the rate of myocardial contraction (+d p /d t), and the pressure rate product (PRP); at 100 microM EPI, LVDP (131+/-9 vs 34+/-7 mmHg), +d p /dt (1515+/-94 vs 542+/-185 mmHg/s), and PRP (37870+/-2471 vs 9498+/-2375 HR x mmHg/min) were all significantly (P<0.05) reduced. EPI also elevated CPP in isolated hearts, decreased levels of myocardial NADPH and nitrite, and dose-dependently relaxed rat aortic rings pre-contracted with KCl. Electrophysiological analysis of single ventricular myocytes using whole cell clamp showed EPI to dose-dependently (100 n M-100 microM) and reversibly inhibit L-type channel currents carried by Ba2+ (IBa) (IC50=42+/-6 microM) by as much as 50%. At 30 microM, EPI shifted the steady-state inactivation curve to more negative potentials (V50=-26.6 mV vs -38.0 mV), thereby accelerating the decay of IBa during depolarization. These results suggest that EPI may act as a L-type Ca2+ channel antagonist with properties similar to those of 1,4-dihydropyridine (DHP) Ca2+ channel blockers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Androsterone / physiology*
  • Animals
  • Calcium / metabolism*
  • Calcium Channel Blockers*
  • Calcium Channels, L-Type / metabolism*
  • Dehydroepiandrosterone / metabolism
  • Hypoxia
  • Male
  • Myocardial Contraction
  • Myocardium / metabolism
  • Myocytes, Cardiac / metabolism*
  • NADP / metabolism
  • Nitrites / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Recovery of Function
  • Testosterone / metabolism


  • Calcium Channel Blockers
  • Calcium Channels, L-Type
  • Nitrites
  • Testosterone
  • Dehydroepiandrosterone
  • NADP
  • Androsterone
  • Calcium