The contribution of prostanoids to endothelium-dependent vasodilatation in the digital circulation of women with primary Raynaud's disease

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 premenopausal 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.