Yonsei Med J.  2003 Dec;44(6):1027-1033. 10.3349/ymj.2003.44.6.1027.

Testosterone Causes Simultaneous Decrease of [Ca2+]i and Tension in Rabbit Coronary Arteries: by Opening Voltage Dependent Potassium Channels

• Won EK
• Won JE
• Kwon SC
• Lee YH
• Nam TS
• Ahn DS

• KMID: 1091044
• DOI: http://doi.org/10.3349/ymj.2003.44.6.1027

Abstract

The relationship between the level of testosterone and the incidence of coronary heart disease is still controversial in the view of the results of clinical and epidemiologic studies. This uncertainty might be partly due to relatively small number of experimental studies undertaken to investigate the cellular mechanism underlying the vascular responses to testosterone. To further investigate the cellular mechanisms of testosterone with respect to vascular response, we investigated the effect of testosterone on contractility and intracellular Ca2+ regulation in a rabbit coronary artery and evaluated the underlying mechanism of testosterone-induced changes of coronary vascular tone by using various pharmacological blockers. Testosterone was found to relax rabbit coronary arteries in a dose-dependent manner, and no significant difference was found in the relaxation response to testosterone with or without endothelium. Similar results were obtained in male and non-pregnant female rabbit coronary arteries. The relaxation response of rabbit coronary arteries to testosterone was greater for PGF2alpha-contracted rings than for KCl contracted rings, which suggest the involvement of K+ channels. Furthermore, the relaxation response to testosterone was significantly reduced by 4-aminopyridine, a sensitive blocker of voltage dependent K+ channels, but not by low doses of tetraethylammonium or iberiotoxin, a Ca2+ activated K+ channel blocker. Testosterone simultaneously reduced the intracellular Ca2+ concentration ([Ca2+]i) and tension, and 4-AP effectively antagonized the testosterone-induced change of [Ca2+]i and tension. Therefore, it may be concluded that the stimulation of voltage dependent K channels is responsible, at least in part, for the testosterone-induced relaxation of rabbit coronary arteries.

Keyword

Testosterone; voltage dependent K+ channels; rabbit coronary artery; 4-aminopyridine; intracellular Ca2+

MeSH Terms

Androgens/*pharmacology
Animals
Arteries/drug effects
Calcium/*metabolism
Coronary Vessels/*drug effects
Female
Intracellular Membranes/*metabolism
Male
Osmolar Concentration
Potassium Channels, Voltage-Gated/drug effects/*metabolism
Rabbits
Support, Non-U.S. Gov't
Testosterone/*pharmacology
*Vasodilation