In 15 women with PR (primary Raynaud's) disease and in 15 matched control women, ACh (acetylcholine) was delivered by iontophoresis to the dorsum of the finger (seven 20 s pulses of 0.1 mA, followed by one 20 s pulse of 0.2 mA, applied at 60 s intervals). Cutaneous RCF (red cell flux) was recorded from the same site by the laser Doppler technique. ACh evoked progressive increases in RCF that were comparable in pre- and post-menopausal women with PR [maxima of 294±113 and 259±59 pu (perfusion units) respectively, n =7 and 8 respectively], and in pre-menopausal controls (225±92 pu, n =7), but smaller in post-menopausal controls (140±63 pu, n =8; P <0.05). Aspirin (600 mg, orally), a COX (cyclo-oxygenase) inhibitor, potentiated the ACh-evoked dilator responses in pre- and post-menopausal women with PR (343±129 and 311±48 pu respectively) and post-menopausal controls (277±124 pu; P <0.05), but had no effect in pre-menopausal controls (225±92 pu). These results suggest that vasoconstrictor COX products limit ACh-evoked endothelium-dependent cutaneous dilatation in the digits in pre- and post-menopausal women with PR and in post-menopausal, but not pre-menopausal, control women. We propose that PR disease is associated with abnormality in the ability of oestrogen to modulate the synthesis of endothelium-dependent vasodilator and/or vasoconstrictor COX products.

1. Primary Raynaud's phenomenon is characterized by white fingers and toes with impaired perfusion in response to cold or emotional stress. The aetiology has not been clarified. In previous studies we have demonstrated a season-linked inability in women with primary Raynaud's phenomenon to raise their plasma cGMP levels in response to whole-body cooling, suggesting a dysfunction of the l-arginine—NO—cGMP pathway. To further elucidate the possibility of such a defect in patients with primary Raynaud's phenomenon, we determined flow-mediated dilatation of the brachial artery. 2. Twenty-two premenopausal, non-smoking women with primary Raynaud's phenomenon (mean age 39 ± 8 years) and 23 healthy controls (mean age 41 ± 7 years) were studied during two winter weeks. The diameter of the right arm brachial artery was measured by high resolution ultrasonography, at rest and during reactive hyperaemia. The investigation was conducted both with the participants at rest at room temperature and after 40 min of whole-body cooling. 3. Both study groups showed a marked attenuation of flow-mediated dilatation during whole-body cooling, which could partly but not solely be explained by a decreased shear rate. There was, however, no significant difference in flow-mediated diameter ( D ) increase (% flow-mediated dilatation; Δ D/D × 100) between primary Raynaud's phenomenon and controls, either at room temperature (7.8 ± 0.8 and 9.0 ± 0.8) or in response to whole-body cooling (3.8 ± 1.2 and 4.4 ± 0.7). 4. Thus, whole-body cooling markedly impairs flow-mediated dilatation in women. Flow-mediated dilatation is, however, not decreased in women with primary Raynaud's phenomenon at room temperature or during whole-body cooling, indicating that this particular aspect of endothelial function is not impaired in this setting.