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Clin Sci (Lond). 2006 Oct;111(4):265-74.

Effect of testosterone on ex vivo vascular reactivity in man.

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1
Department of Cardiology Research, Royal Hallamshire Hospital Sheffield, Sheffield S10 2JF, UK.

Abstract

Testosterone is reported to have an acute vasodilating action in vitro, an effect that may impart a favourable haemodynamic response in patients with chronic heart failure. However, the effect of chronic testosterone exposure on general vascular reactivity is poorly described. In the present study, fresh subcutaneous resistance arteries were obtained from patients with heart failure (n=10), healthy controls (n=9) and men with androgen-deficiency (n=17). All arteries were studied using a wire myograph to examine the effect of cumulative additions of testosterone (1 nmol/l-100 micromol/l) compared with vehicle control following maximal pre-constriction with KCl (1-100 micromol/l). The vascular reactivity of arteries from androgen-deficient patients was examined further by recording tension concentration curves to cumulative additions of noradrenaline (1 nmol/l-100 micromol/l) and U46619 (1-300 nmol/l), followed by relaxation concentration curves to additions of ACh (acetylcholine; 10 nmol/l-30 micromol/l) and SNP (sodium nitroprusside; 10 nmol-30 micromol/l) respectively. In all cases, statistical analysis was performed by ANOVA. Patients with proven androgen-deficiency were treated according to clinical recommendations for a minimum of 3 months and further arteries (n=19) were taken for experimentation using the same protocol. In all groups, testosterone was confirmed to be an acute concentration-dependent vasodilator at concentrations > or =1 micromol/l (P=0.0001). The dilating effect of testosterone was augmented in patients with androgen-deficiency prior to treatment, and this effect was abrogated following appropriate testosterone replacement. Testosterone therapy significantly reduced the normal vascular dilating response to ACh and SNP (P<0.01) and significantly increased the contractile response to noradrenaline (P<0.01), but not U46619. Testosterone is an acute dose-dependent vasodilator of resistance arteries. Physiological testosterone replacement attenuates general vascular reactivity in androgen-deficient subjects. The numerous perceived benefits of testosterone replacement may be offset by a decline in vascular reactivity and, therefore, further studies and careful monitoring of patients is recommended.

Comment in

PMID:
16722820
DOI:
10.1042/CS20050354
[Indexed for MEDLINE]

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