Testosterone relaxes human internal mammary artery in vitro

Preliminary clinical studies of testosterone therapy in male patients with coronary artery disease raised promising results. However, there is no study on in vitro effects of testosterone in human isolated arteries. We investigated the effect of testosterone on contractile tone of human isolated internal mammary artery. The responses in human internal mammary artery (IMA) were recorded isometrically by a force-displacement transducer in isolated organ baths. Testosterone (10 nM to 100 mu M) was added cumulatively to organ baths either at rest or after precontraction with KCl (68 mM) and PGF(2 alpha) (10 mu M). Testosterone-induced relaxations were tested in the presence of cyclooxygenase inhibitor indomethacin (10 mu M), nitric oxide synthase inhibitor N-omega-nitro-L-arginine methyl ester (L-NAME, 1 mu M), nonselective large-conductance Ca2+-activated and voltage-sensitive K+ channel inhibitor tetraethylammonium (TEA, I mM), ATP-sensitive K+ channel inhibitor glibenclamide (GLI, 100 mu M), and voltage-sensitive K+ channel inhibitor 4-aminopyridine (4-AP, I mM). Testosterone produced relaxation in human IMA (E-max 33% and 41% of KCl- and PGF(2 alpha)-induced contraction, respectively). Vehicle had no significant relaxant effect. Except for TEA, the relaxation at low concentrations is not affected by either K+ channel inhibitors (GLI and 4-AP) or L-NAME and indomethacin. We report for the first time that supraphysiological concentrations of testosterone induce relaxation in IMA. This response may occur in part via large conductance Ca2+-activated K+ channel-opening action.