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Testosterone relaxes coronary arteries by opening the large-conductance, calcium-activated potassium channel

V P Deenadayalu1, R E White, J N Stallone

  • 1Department of Physiology and Biophysics, Wright State University School of Medicine, Dayton, Ohio 45435-0927, USA.

American Journal of Physiology. Heart and Circulatory Physiology
|September 15, 2001
PubMed

Insights

Testosterone relaxes coronary arteries by opening large-conductance, calcium- and voltage-activated potassium (BK(Ca)) channels in smooth muscle cells. This mechanism, independent of the endothelium, involves potassium efflux and may relate to cGMP accumulation.

Area of Science:

  • Cardiovascular Physiology
  • Endocrinology
  • Molecular Biology

Background:

  • Cardiovascular diseases are perceived as a male health issue, with testosterone often implicated negatively.
  • The precise cellular and molecular mechanisms of testosterone's vascular effects remain largely unknown.
  • Existing research lacks robust experimental support for detrimental cardiovascular effects of testosterone.

Purpose of the Study:

  • To investigate the acute effects of testosterone on porcine coronary artery smooth muscle.
  • To elucidate the cellular and molecular mechanisms underlying testosterone-mediated vascular responses.
  • To determine if testosterone directly impacts coronary artery function.

Main Methods:

  • Tissue-level contractile studies on porcine coronary arteries.
  • Cellular electrophysiology using patch-clamp techniques on single coronary myocytes.
  • Pharmacological inhibition of specific ion channels to assess their role.

Main Results:

  • Testosterone and dihydrotestosterone induced relaxation of coronary arteries via an endothelium-independent pathway.
  • This relaxation was linked to potassium (K+) efflux from smooth muscle cells.
  • Testosterone was found to directly open large-conductance, calcium- and voltage-activated potassium (BK(Ca)) channels in coronary myocytes.
  • Inhibition of BK(Ca) channels significantly reduced testosterone-induced vasodilation.

Conclusions:

  • Testosterone primarily relaxes porcine coronary arteries by activating BK(Ca) channels in coronary myocytes.
  • This vasorelaxation mechanism is associated with potassium efflux and potentially cGMP accumulation.
  • The findings offer a novel molecular explanation for testosterone-induced vasodilation observed in experimental and clinical studies.

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