Characterization of the vasodilatory action of testosterone in the human pulmonary circulation

Alyson M Smith¹, Robert T Bennett², T Hugh Jones¹, Mike E Cowen², Kevin S Channer³, Richard D Jones¹

¹Academic Unit of Diabetes, Endocrinology and Metabolism, The University of Sheffield, Sheffield, UK; ²Department of Cardiothoracic Surgery, Castle Hill Hospital, Hull and East Yorkshire Hospitals NHS Trust, Cottingham, UK; ³Department of Cardiology, Royal Hallamshire Hospital, Sheffield, UK

Aim: To assess for the first time the vasodilatory effect of testosterone in the human pulmonary circulation utilizing both isolated human pulmonary arteries and isolated perfused human lungs. In addition, a secondary aim was to determine whether there was any difference in the response to testosterone dependant upon gender.

Methods: Isolated human pulmonary arteries were studied by wire myography. Vessels were preconstricted with U46619 (1 nM–1 μM) prior to exposing them to either testosterone (1 nM–100 μM) or ethanol vehicle (<0.1%). Isolated lungs were studied in a ventilated and perfused model. They were exposed to KCl (100 mM), prior to the addition of either testosterone (1 nM–100 μM) or ethanol vehicle (<0.1%).

Results: Testosterone caused significant vasodilatation in all preparations, but a greater response to testosterone was observed in the isolated perfused lungs, 24.9 ± 2.2% at the 100 μM dose of testosterone in the isolated pulmonary arteries compared to 100 ± 13.6% at the 100 μM dose in the isolated perfused lungs. No significant differences in the response to testosterone were observed between sexes.

Conclusion: Testosterone is an efficacious vasodilator in the human pulmonary vasculature and this is not modulated by patient sex. This vasodilator action suggests that testosterone therapy may be beneficial to male patients with pulmonary arterial hypertension.

Keywords: human, pulmonary circulation, pulmonary hypertension, sex hormone, testosterone, vasodilation