Testosterone Relaxes Human Internal Mammary Artery In Vitro

Abstract

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.

Hormonal effects on blood vessels

“…[106][107][108] The involvement of potassium channels in testosterone-induced vasodilatation has also been studied by many researchers. [109][110][111] Cairrao et al 112 reported that an AR antagonist, flutamide, and an adenosine triphosphate-sensitive potassium-channel inhibitor, glibenclamide, had no influence on the testosterone relaxant effect, whereas a voltage-sensitive potassium-channel inhibitor, 4-aminopyridine, decreased this effect of testosterone. Opening of voltage-sensitive potassium channels induces hyperpolarization of the plasma membrane, which in turn may lead to the closing of L-type Ca2+ channels.…”

Testosterone: a vascular hormone in health and disease

“…Similarly, radial artery isolated from patients undergoing bypass surgery was shown to vasodilate in response to testosterone after pre-contraction with potassium chloride or phenylephrine (Seyrek et al 2007). The same group had previously found that testosterone relaxes isolated human internal mammary artery pre-contracted with potassium chloride or prostaglandins (Yildiz et al 2005).…”

Pharmacology of Arterial Grafts for Coronary Artery Bypass Surgery

“…sponse to testosterone may occur in via large-conductance Ca 2+ -activated K + channelopening action [112]. Clinical studies of testosterone therapy in male patients with coronary artery disease raised promising results.…”

“…Testosterone may exert vasorelaxant effects on several vascular tissues [112][113][114][115][116][117][118][119]. We have studied effects of testosterone in the human IMA and found that vasorelaxant re-…”