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

OBJECTIVES: 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. AIM: 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. METHOD: 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. RESULTS: 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. CONCLUSION: 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.