Testosterone-induced vasodilatation of isolated human mesenteric resistance arteries is independent of the vascular endothelium   RD Jones, KO Rowell, PJ Pugh, AJ Shorthouse, IA Adam, TH Jones & KS Channer. Division of Genomic Medicine, University of Sheffield, UK & Department of Cardiology, Royal Hallamshire Hospital, Sheffield, UK.	Print Abstract Search PubMed for: Jones RD Rowell KO Pugh PJ Shorthouse AJ Adam IA Jones TH Channer KS

Testosterone (T) reduces myocardial ischaemia in men with coronary artery disease (English et al., 2000), and has a direct coronary vasodilatory activity (Webb et al., 1999). T also improves symptoms and exercise capacity in men with heart failure (Pugh et al., 2002), and has been demonstrated to lower peripheral vascular resistance in these individuals (Pugh et al. 2003), consistent with a systemic vasodilatory activity. However, the vasodilatory mechanism of action of T has yet to be investigated in the human vasculature.

Mesenteric tissue was obtained from male patients (n=14, age= 70±2), undergoing gastrointestinal surgery for removal of bowel cancer. The study was approved by the local Ethics Committee and all patients gave full written informed consent. Mesenteric resistance arteries (MRA, n=28, diameter = 385±20µm) were dissected, and the endothelium removed from half of the vessels by gently rubbing the intra-luminal surface. Vessels were then loaded in a wire myograph at a tension of 11.2±2.3 mN, equivalent to 97.1±1.6mmHg, and maintained at 37°C in physiological saline solution bubbled with 95% O₂, 5% CO₂ to sustain a pH of 7.4. Vessel viability and reproducibility was confirmed by two exposures to potassium chloride (KCl, 70mM). Endothelial integrity was assessed by exposure to acetylcholine (ACh, 1µM) following preconstriction with noradrenaline (NA, 10µM).Vessels were then exposed to KCl (0.1-100µM) followed by cumulative additions of T (1nM-100 µM) or ethanol vehicle (Eth). Vessels were washed and then T-induced vasodilatation, which may contribute to the clinical benefits associated with T therapy in men with heart disease, is not mediated via endothelial-derived dilators in isolated human MRA.

T-mediated vasodilatation of isolated human MRA occurred at concentrations >3µM and was statistically similar in endothelial intact and denuded vessels (Table 1).

Table 1 - Mean (S.E.M.) contractions to KCl and NA (mN), and dilatation to ACh, Eth and T (% relaxation of precontractile tone) NS = not significant, * p<0.001 compared to Eth via Mann-Whitney U Test.

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