Vascular tone is dependent on the balance of vasoconstrictor and vasodilator influences. Systemic hypoxia induces vasodilatation in skeletal muscle (Coney et al. 2004). This effect is observed when the hypoxia is applied acutely for 5min and also persists when the hypoxia is maintained chronically (CH) for up to 3 days. A role for adenosine and nitric oxide has been proposed for this effect (Walsh & Marshall, 2006). However, changes also occur in vasoconstrictor mechanisms and 3-4 weeks of CH results in attenuated adrenergic vasoreactivity of aortic rings (Doyle & Walker, 1991) and a reduction in sympathetically-evoked vasoconstriction in vivo (Coney et al. 2004). In this study we hypothesised that there might be an effect on vasoreactivity in the first few days of CH which may contribute to the tonic vasodilatation in skeletal muscle vessels. Male Wistar rats (200-300g) were divided into 3 groups: Normoxic (N; n=13), 1 day CH (1CH; n=12) and 3 day CH (3CH; n=5). CH was induced in an hypoxic chamber maintained at 12% O₂ (Coney et al. 2004). Femoral arteries were excised under terminal anaesthesia (halothane 1-3% in O₂) rings (3-4mm length) were mounted on a Mulvany myograph bubbled with 95% O₂:5% CO₂ and normalised to 100mmHg. Responses to the α₁-agonist, phenylephrine (PE; 10, 100 & 300µM) were measured. The maximum constriction that could be totally blocked by phentolamine (1mM) was determined and all tensions expressed as a percentage of this maximum. Data are presented as mean±SEM and analysed by ANOVA and post hoc test. Significance was taken as P<0.05. The maximum tension recorded was not significantly different between all groups. In rings from N rats, PE induced a dose-dependent increase in tension (34±2, 52±2 and 68±2%, respectively). Rings from 1CH also showed a dose-dependent increase which was significantly increased, compared to N rings, at 10 and 100µM (50±3 and 67±3% respectively) but was not significantly different at 100µM (71±4%). In contrast, 3CH rings showed no dose-dependent increase (29±3, 33±3 and 41±4% respectively) with all responses significantly depressed compared to N rings. Our data demonstrates that the ability of α₁-adrenoceptors to induce vasoconstriction in rat femoral arteries can be modulated differentially after 1 and 3 days of chronic hypoxia. Specifically we propose that, after 1 day of CH, attenuated adrenergic vasoreactivity does not contribute to the tonic vasodilatation seen at this time but it may contribute after 3 days of CH.