Inflammation plays a central pathogenic role in the initiation and progression of coronary atheroma and its clinical consequences.

Objective: Testicular feminised (Tfm) mice express a non-functional androgen receptor, and also have reduced levels of circulating testosterone. Recent studies support a cardio-protective role for testosterone since it elicits systemic and pulmonary vasodilatation. The aim of the present study was to determine whether androgen insensitivity and hypotestosteronaemia in the Tfm mouse are associated with abnormal vascular reactivity or hormone status. Methods: Adult male Tfm and littermate control mice were killed and the blood collected. Femoral (diameter range = 183 -508 mm) and pulmonary (diameter range = 320-816 mm) arteries were dissected and loaded in either a wire or pressure myograph, at 100 mmHg or 17.5 mmHg respectively. Pharmacological assessment of the vasoreactivity to potassium chloride (KCl, 80 mmol/l) and either noradrenaline (NA, 1 nmol/l -100 mmol/l) and acetylcholine (ACh, 0.1 -100 mmol/l) or testosterone (1 nmol/l -100 mmol/l) was then made. Results: Tfm mice had reduced levels of testosterone (1.8^0.3 nmol/l) compared with controls (9.3^2.0 nmol/l, P , 0:001Þ and elevated levels of cholesterol (3.6+0.1 mmol/l) compared with controls ð3:2 þ 0:1 mmol=l; P , 0:05Þ: Femoral arteries from Tfm mice exhibited reduced vasoconstriction to 80 mmol/l KCl ð3:27^0:23 mN=mmÞ compared with vessels from controls ð4:44^0:41 mN=mm; P , 0:05Þ; and reduced endothelial-dependent vasodilatation to 0.1-100 mmol/l ACh ð23:3^3:6% relaxation) compared with vessels from controls ð41:6^5:4% relaxation, P , 0:05Þ: Vasoconstriction to NA (1 nmol/l -100 mmol/l) and vasodilatation to testosterone were unaffected. Conclusions: Androgen receptor deficiency and hypotestosteronaemia in the Tfm mouse reduced endothelial function and impaired voltage-operated calcium channel activity, which may pre-dispose to cardiovascular disease. Testosterone-induced vasodilatation was unaffected, demonstrating no involvement of the androgen receptor in this response.

Consequently this data implicates IL-1beta and IL-10 in the pathogenesis of CAD and suggests that testosterone may regulate IL-1beta activity in men with CAD.

No abstract

The efficacy of first and subsequent DCCV procedures is similar, achieving a similar proportion of SR maintenance at 1 year. However, the benefits of AAD therapy are the greatest following first time procedures. Concomitant AAD therapy should be considered for all first time procedures for persistent AF.