Endocrine Abstracts (2004) 7 P66

Testosterone-induced vasodilatation of isolated human mesenteric and pulmonary resistance arteries is independent of the vascular endothelium

RD Jones1, KO Rowell1, PJ Pugh2, AJ Shorthouse3, IA Adam3, R Vaughan4, G Rocco4, DN Hopkinson4, KS Channer2 & TH Jones1

1Hormone & Vascular Biology Group, Academic Unit of Endocrinology, The University of Sheffield, Sheffield, UK; 2Department of Cardiology, Royal Hallamshire Hospital, Sheffield, UK; 3Department of Gastrointestinal Surgery, Royal Hallamshire Hospital, Sheffield, UK; 4Department of Cardiothoracic Surgery, Northern General Hospital, Sheffield, UK.

Testosterone reduces myocardial ischaemia in men with coronary artery disease, and improves symptoms and exercise capacity in men with heart failure, effects proposed to be due to testosterone-induced coronary, systemic and pulmonary vasodilatation. Endothelial-independent calcium channel antagonism is proposed as the effector mechanism from in vitro animal studies, but this has yet to be confirmed in humans.

In the present study we have investigated the vasodilatory action of testosterone in isolated human mesenteric resistance arteries (MRA) and pulmonary resistance arteries (PRA). The study was approved by the Sheffield Teaching Hospitals NHS Trust Ethics Committee. Mesenteric and lung tissue was obtained at surgery from male patients (n=14, age = 70plus/minus2, and n=10, age = 66plus/minus3 respectively). MRA and PRA were dissected and the endothelium removed from half by gently rubbing the intra-luminal surface. Endothelial-denuded (end(-)) MRA (n=16, diameter = 393plus/minus31micrometre), endothelial intact (end(+)) MRA (n=12, diameter = 376plus/minus23micrometre), end(-)PRA (n=7, diameter = 360plus/minus42micrometre) and end(+)PRA (n=7, diameter = 415plus/minus70micrometre) were loaded in a wire myograph and maintained at their in vivo pressure in oxygenated physiological saline at 37degC. Endothelial status was confirmed by exposure to acetylcholine (10-6M) following preconstriction with noradrenaline (10-5M). Vessels were then exposed to KCl (10-4M-10-1M) followed by cumulative additions of testosterone (10-9M-10-4M) or ethanol vehicle, washed and then re-exposed to KCl followed by the alternative agent.

Testosterone (10-6M-10-4M) induced vasodilatation in all vessels, but exhibited a lower efficacy in PRA compared to MRA; 58.1plus/minus5.5% versus 95.0plus/minus8.1% (P<0.001). The maximal response was statistically similar in end(+) and end(-) vessels; end(+)MRA = 95.0plus/minus8.1% and end(-)MRA = 88.2plus/minus8.3% (P=0.57), end(+)PRA = 58.1plus/minus5.5% and end(-)PRA = 47.4plus/minus6.1% (P=0.21).

Testosterone-induced vasodilatation, which may contribute to the clinical benefits associated with testosterone therapy in men with heart disease, is not mediated via endothelial-derived dilators.