Contributions of cyclooxygenase (COX) and NO synthase (NOS) pathways to endothelium‐dependent dilatation in the finger of women

Abstract

We tested the roles of COX and NOS in finger vasodilatation evoked by iontophoresis of acetylcholine (ACh), using laser Doppler fluximetry. In 12 women in the low oestrogen (E2) phase of the menstrual cycle, aspirin (600mg p.o) decreased baseline finger red cell flux (RCF) from 55.0±7.8 to 30.6±5.5* perfusion units (pu; *: P<0.05), and the ACh‐evoked response from +296.8±23.9 to +251.4±24.4* pu. In the high E2 phase, COX inhibition decreased baseline from 68.0 ± 13.8 to 38.4 ± 8.1*, but had no effect on the ACh response (259.5±27.4 vs 251.2±23.3 pu). On different days, NOS inhibition with L‐NAME had no effect on baseline RCF in the low, or high E2 phase. In the low E2 phase, the ACh response was unchanged (+228.26±25.8 vs 225.6±21.3pu), but aspirin then decreased the response further to 175.9±17.6*pu. In the high E2 phase, L‐NAME increased the ACh response from +198.1±23.7 to +229.2±27.4*pu; COX inhibition restored it to +202.8±27.8pu. We propose that in the finger, NOS generates both NO and O2− and thereby, ONOO− which inhibits PGI2 synthase. E2 facilitates NOS and PGI2 synthase such that when E2 is high, PGI2 contributes to endothelium‐dependent finger dilatation only after NOS inhibition.