The vasodilatory action of testosterone in isolated perfused human lungs

Alyson M. Smith1,2, Robert T. Bennett3, Richard D. Jones1, T. Hugh Jones1,4, Michael E. Cowen3 & Kevin S. Channer2,5. 1Academic Unit of Endocrinology, Division of Genomic Medicine, The University of Sheffield; 2Department of Cardiology, Royal Hallamshire Hospital, Sheffield; 3Department of Cardiothoracic Surgery, Castle Hill Hospital, Cottingham; 4Centre for Diabetes and Endocrinology, Barnsley Hospital NHS Foundation Trust; 5Faculty of Health and Well-being, Sheffield Hallam University.

Testosterone has been shown to be a coronary vasodilator, with beneficial effects in angina (English et al, 2000) and chronic heart failure (Pugh et al, 2004). This study investigated the potential vasodilatory effects of testosterone in the pulmonary circulation, with an aim of being a potential treatment in pulmonary hypertension.

Lung samples were obtained from 8 patients (4 male, 4 female, mean age 61.1 yrs ± 5.6) undergoing elective lung (n=1) or lobe (n=7) resection and studied as an isolated ventilated and perfused system (methodology described in Bennett et al., 2004). The study was approved by the local ethics committee and all patients gave informed consent. The pulmonary arterial and bronchial systems were cannulated and the lungs were ventilated with room air (Tidal volume 100-300ml/min) and perfused with Krebs bicarbonate buffer (1L, 100-300ml/min). Perfusion pressure (mmHg) was recorded continuously via a pressure transducer. The pulmonary vasculature was preconstricted with potassium chloride, KCl (70mM) to confirm viability followed by cumulative additions of ethanol vehicle (100-700uL). The pulmonary circulation was then washed by perfusing with fresh buffer and the addition of KCl (70mM) was repeated followed by increasing concentrations of testosterone (1nM -100uM).

Results are shown in Table 1 as: Percentage relaxation mean ± standard error mean. A statistically significant relaxation to testosterone was seen, compared to the control vehicle ethanol.

Table 1

* P<0.05 via Wilcoxon signed rank test for paired samples.

Conclusion: Testosterone dilates the human pulmonary circulation at micromolar concentrations. This may be translated into improved pulmonary haemodynamics and symptoms in patients with pulmonary hypertension.

Bennett RT et al. Thorax 2004; 59:401-407.
English KM et al.Circulation 2000; 102(16): 1906-1911.
Pugh PJ et al.Heart 2004; 90(4): 446-447.