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 microM) was added cumulatively to organ baths either at rest or after precontraction with KCl (68 mM) and PGF2alpha (10 microM). Testosterone-induced relaxations were tested in the presence of cyclooxygenase inhibitor indomethacin (10 microM), nitric oxide synthase inhibitor Nomega-nitro-L-arginine methyl ester (L-NAME, 1 microM), nonselective large-conductance Ca2+-activated and voltage-sensitive K+ channel inhibitor tetraethylammonium (TEA, 1 mM), ATP-sensitive K+ channel inhibitor glibenclamide (GLI, 100 microM), and voltage-sensitive K+ channel inhibitor 4-aminopyridine (4-AP, 1 mM). Testosterone produced relaxation in human IMA (Emax 33% and 41% of KCl- and PGF2alpha-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.
Yildiz
Oguzhan
O
Department of Pharmacology, Gulhane Military Medical Academy, Ankara, Turkey. oyildiz@gata.edu.tr
Seyrek
Melik
M
Gul
Husamettin
H
Un
Ismail
I
Yildirim
Vedat
V
Ozal
Ertugrul
E
Uzun
Mehmet
M
Bolu
Erol
E
D006801:Humans; D066298:In Vitro Techniques; D008323:Mammary Arteries / Q000187:drug effects* / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D013739:Testosterone / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology
D013739:Testosterone; D019331:NG-Nitroarginine Methyl Ester