Testosterone acts as an efficacious vasodilator in isolated human pulmonary arteries and veins: Evidence for a biphasic effect at physiological and supra-physiological concentrations

Abstract

Testosterone is recognized to elicit vasodilatation in numerous vascular beds, however to date no study has investigated whether testosterone has this effect in the human pulmonary vasculature. To determine whether isolated human pulmonary arteries and veins dilate in response to testosterone and whether the response differs in relation to gender, endothelial function or location with the pulmonary vasculature. Intralobar pulmonary arteries [no.=44, diameter =581 (349) microm] and veins [no.=27, diameter =573 (302) microm] were dissected from lobectomy samples obtained from male and female patients [no.=40, age =69 (8) yr]. Vessels were mounted in an automated wire myograph, bathed in physiological saline at 37 C and pH 7.4, and loaded to their in vivo pressure. Vessels were preconstricted with noradrenaline (10 microM) and exposed to acetylcholine (1 microM) to assess endothelial function, washed and then preconstricted with potassium chloride (1-100 mM) followed by either cumulative concentrations of testosterone (1 nM-100 microM) or ethanol vehicle (<0.1%). Significant marked vasodilatation was seen in all vessels, irrespective of size, gender and endothelial function at micromolar concentrations. Testosterone triggered significant vasodilatation at concentrations > or = 10 nM in pulmonary arteries obtained from males, a response which was not observed in vessels from females. The maximal response at 100 microM was also significantly greater in male pulmonary arteries. Significant vasodilatation was only observed at physiological (nM) concentrations in pulmonary resistance arteries and pulmonary arteries with good endothelial function. Testosterone acts as an efficacious vasodilator in the human pulmonary vasculature, with dilatation observed at physiological concentrations in the male arterial resistance bed, dependent on the presence of an intact endothelium.