[Platelet activation and endothelial factors in standard exercise test before and after menopause]

Postmenopausal lack of estrogens may accelerate cardiovascular atheromatic changes. Standard exercise test (SET) challenges hidden signs of the vascular involvement. Although the test is known not to carry a risk of thromboembolic complications, it may influence plasma concentrations of endothelial and platelet factors. The question is if and to what extend the menopause aggravates the SET induced changes.

Plasma concentrations of nitric oxide, endothelin-1, beta-thromboglobulin and von Willebrand factor activity before, at the maximum exercise and 15 minutes after the SET referred to, as a recovery time were estimated.

SET was performed according to Bruce protocol in group of 31 premenopausal and 57 postmenopausal women. Standard RIA kits for plasma beta-thromboglobulin (beta-TG) (Boehringer Mannheim) and endothelin-1 (Et-1) (Blotrack) concentration were used. The von Willebrand factor (vWF) activity was assayed by ELISA system (Boehringer Manheim). Plasma nitric oxide (NO) concentration was calculated from nitrides/nitrates levels, by Griess reaction, modified by use of NADPH reductase.

Mean plasma levels of beta-TG, Et-1, NO and vWF activity do not differ between pre and postmenopausal women. The standard exercise test significantly increases both beta-TG plasma concentration and vWF activity (p < 0.00001). During the 15 minutes rest period the changed values do not return to preexercise levels. Neither plasma NO nor Et-1 plasma concentrations change during the exercise test. There was a similar increase in beta-TG plasma levels and vWF activity during the SET in pre- and postmenopausal women and a slighter increase of plasma Et-1 levels in postmenopausal women (p < 0.04). The close relationships between NO plasma concentration and both vWF activity (p < 0.002) and vascular endothelial growth factor (VEGF) level (p < 0.04) were observed in postmenopausal women. The vWF activity in postmenopausal; women inversely correlates with insulin-like growth factor-I (IGF-I) concentration (p < 0.001). In premenopausal women the important modulators of vWF activity were: body mass (p < 0.04), serum total cholesterol (p < 0.02) and sex hormone binding globulin (SHBG) levels (p < 0.04). The postmenopausal beta-TG increase during SET depends on body mass (p < 0.02), whereas the preexercise levels seem to be related to VEGF level (p < 0.03) and inversely to Et-1 (p < 0.007) and dehydroepiandrosterone sulfate (DHEAS) concentration (p < 0.03) Both the basal and stimulated by exercise vWF activity are higher in obese women (p < 0.003), but the net increase is larger in lean group (BMI < 30 kg/m2). In premenopausal women plasma NO concentration depends on 17 beta-estradiol serum level (p < 0.02). The higher VEGF (p < 0.01) levels as well as vWF activity was observed (p < 0.03) in hypercholesterolemic women.

The standard exercise test increases the procoagulatory von Willebrand factor activity so as the platelets activity (beta-thromboglobulin concentration) in both pre and postmenopausal women. The slight endothelin-1 rise has been found at the maximum exercise in postmenopausal women. The close relation between plasma nitric oxide and endothelin-1 levels was found in postmenopausal women. Obesity and hypercholesterolemia may contribute to the observed changes.