Endothelial function in healthy women and in women with primary Raynaud´s phenomenon

Abstract

Endothelial function, assessed as the vasoregulatory effect of nitric oxide (NO), was examined (a) in healthy women with respect to season, time of day, and time in the menstrual cycle, (b) in men, to examine the influence of gender, and (c) in women with primary Raynaudís phenomenon (PRP). To this object, plasma concentrations and urinary excretion of nitrate and cyclic guanosine 3í:5í-monophosphate (cGMP) were determined. In addition, endothelium-dependent vasodilation was assessed by ultrasound determinations of flow-mediated vasodilation (FMD%) in the brachial artery that was contrasted with endothelium-independent vasodilation i.e. nitroglycerine-induced vasodilation (NTG%). Plasma concentrations and urinary excretion of nitrate and cGMP did not display seasonal, diurnal, or menstrual cycle variation in healthy women. FMD% and NTG% were stable throughout the menstrual cycle, but displayed separate patterns of diurnal variation. Determinations of nitrate, cGMP, FMD%, and NTG% did not reveal any gender differences. Women with PRP displayed a season-dependent disturbance in their plasma cGMP response to whole body cooling (WBC). Plasma cGMP levels in healthy women increased in response to WBC both in the summer and in the winter, whereas women with PRP displayed this ìhealthyî pattern only in the summer. Plasma nitrate levels and FMD% did, however, not change in response to WBC, either in PRP or in controls. These data indicate that blood and urine samplings for nitrate- and cGMP-determinations in healthy women do not require standardisation for season, time of day, phase in the menstrual cycle, or gender. FMD% examinations do not have to be standardised for time in the menstrual cycle or for gender, but should be performed at the same time of the day to minimise the physiological variations. The idea of a season-linked endothelial dysfunction in PRP patients, raised by the inadequate plasma cGMP response to WBC in the winter, was not supported by assessments of plasma nitrate and FMD%. However, the season linked disturbance of the plasma cGMP response to WBC in PRP, was reproducible, and could represent an important clue in revealing the culprit lesion/-s in PRP.