Background: Current evidence suggests that testosterone acts as a vasodilator in several vascular beds. This may have implications for men who are androgen deficient, in whom vascular reactivity may be impaired. We have studied vascular responses in vitro in femoral arteries from testicular feminised mice (Tfm), which lack a functional androgen receptor and are consequently androgen resistant and have reduced circulating levels of testosterone. Methods: Femoral arteries from male Tfm (n=8) and littermate controls (XY) (n=8) were studied in a pressure myograph under no-flow conditions. Vessels were gradually pressurised to 100mmHg and viability confirmed by change in diameter in response to KCl 80mM. Concentration-response curves to noradrenaline (NA) and acetylcholine (ACh) were constructed. The effect of testosterone (10nM to 100uM) was then assessed by cumulative addition of testosterone to the organ bath, after pre-contraction with NA (10uM). Vessel responses were analysed by ANCOVA and between-group comparisons made by Student's t test. Data as mean(SD). Results: Mean age and vessel diameter were similar in the two groups (71.3(6.5) days v 75.3(6.5) days, p=0.2; 227.6(50.3)um v 268.6(46.9)um, p=0.11). There was no significant difference in vessel distensibility, nor in maximal change in vessel diameter in response to KCl, NA and ACh between Tfm and XY mice (-129.1(37.8)um v -149.8(42.1)um, p=0.3; -170.6(50.1)um v 185.3(15.2)um, p=0.4; 18.9(9.9)% v 23.2(13.4)%, p=0.4). Addition of testosterone produced a significant concentration-dependent dilatation (p<0.0001), which was similar in both groups (maximum dilatation 64(18.6)% v 64.2(19.7)%, p=0.8). The lowest concentration producing significant dilatation was 300uM (4.1% dilatation, p<0.01). Conclusion: Vessel responses to stretch, contractile agonists and endothelium-dependent dilatation appear to be independent of the nuclear androgen receptor. Testosterone induced vessel dilatation at near physiological concentrations to a similar extension in both groups, suggesting that the vascular action of testosterone is also independent of the nuclear androgen receptor.
03 - 04 Dec 2001
Society for Endocrinology