Disorders associated with increased vasoconstriction (migraine, Primary Raynaud’s disease) are prevalent in women of child bearing age when compared to men; implicating oestrogen (E₂; Silberstein & Merriam, 1991; Maricq et al. 1986). We have previously shown that in female rats in the low E₂ phases of the oestrous cycle, acute systemic hypoxia induces muscle vasodilatation and a fall in arterial blood pressure (ABP) but acute administration of E₂ attenuates these responses, suggesting E₂ may facilitate the vasoconstrictor influences of systemic hypoxia (Tomlinson et al. 2006). We have now investigated whether E₂ facilitates α₁-adrenoreceptor-mediated vasoconstriction during systemic hypoxia by releasing a vasoconstrictor COX product, thromboxane A₂/prostaglandin H₂ (TXA₂/PGH₂) as suggested by in vitro experiments on the aorta (Fulton & Stallone, 2002). Experiments were performed on anaesthetised (Saffan; 4-8mg.kg.^-1hr^-1 I.V.) female Wistar rats, in the low E₂ phases of the oestrous cycle as determined by vaginal smears. The response evoked by breathing 12% O₂ for 5min was tested before and 30, 60 and 90min after administration of 17β-oestradiol (E₂; 10μg.kg.^-1 I.V.). Group 1 (n=9, 169±4g; mean±SEM) also received SQ 29,548 (SQ; 2mg.kg^-1 bolus and 2mg.kg^-1.hr^-1 continuous infusion I.V.), a TXA₂/PGH₂ receptor antagonist). In Group 2 (n=7; 180±6g) the response to hypoxia was tested before and after the α₁-adrenoreceptor antagonist, prazosin (0.5mg.kg^-1 bolus and 0.8mg.kg^-1.hr^-1 continuous infusion I.V.) and then 30, 60 and 90 min after E₂. ABP and femoral blood flow (FBF) were recorded and femoral vascular conductance (FVC=FBF/ABP) was calculated. In Group 1, the attenuating effect of E₂ on the hypoxia-induced muscle vasodilatation and fall in ABP (see Tomlinson et al. 2006) was abolished by SQ. This suggests that the effect of E₂ on the hypoxic vasodilatation is mediated by a vasoconstrictor effect of TXA₂/PGH₂ receptor stimulation. In Group 2, prazosin reduced baseline ABP (from 117±5 to 81±2mmHg) and caused muscle vasodilatation (Integrated (Int) FVC increased by 1.47±0.66 CU) as expected. Hypoxia still reduced ABP (by 17±4mmHg) and caused muscle vasodilatation (Int FVC increased by 1.87±0.47 CU), but the effect of E₂ on these changes was attenuated. Thus it seems likely that the action of E₂ is partly dependent on α₁-adrenoreceptor stimulation. We propose that in female rats, when endogenous E₂ is low, a further increase in E₂ acutely attenuates the muscle vasodilator and depressor response to hypoxia by facilitating the action of TXA₂/PGH₂, which may be released by α₁-adrenoreceptor stimulation (Fulton & Stallone, 2002).