Irina I Lobysheva1, Sandrine van Eeckhoudt2, Flavia Dei Zotti2, Ahmad Rifahi2, Lucie Pothen2, Christophe Beauloye3, Jean-Luc Balligand4. 1. Institut de Recherche Experimentale et Clinique (IREC), Pole of Pharmacology and Therapeutics (FATH), Université Catholique de Louvain, Brussels, Belgium. Electronic address: Irina.lobysheva@uclouvain.be. 2. Institut de Recherche Experimentale et Clinique (IREC), Pole of Pharmacology and Therapeutics (FATH), Université Catholique de Louvain, Brussels, Belgium. 3. Pole of Cardiovascular Research (CARD), and Departments of Internal Medicine and Cardiovascular Diseases, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Brussels, Belgium. 4. Institut de Recherche Experimentale et Clinique (IREC), Pole of Pharmacology and Therapeutics (FATH), Université Catholique de Louvain, Brussels, Belgium. Electronic address: jl.balligand@uclouvain.be.
Abstract
An increased risk of venous thromboembolism was identified in young women consuming combined contraceptive pills (CP) suggesting a disturbance of vascular homeostasis but the impact of CP on endothelial function and redox status of the vasculature was not thoroughly analyzed. We measured the bioavailability of nitric oxide (NO), a main mediator of vascular homeostasis in a cohort of young female subjects (n=114) and compared the results in users or not of CPs containing ethinyl estradiol and synthetic progestogens. Vascular NO availability was measured by quantification of the heme-nitrosylated hemoglobin (5-coordinate-α-HbNO) concentrations in venous erythrocytes using Electron Paramagnetic Resonance spectroscopy (EPR). Vascular oxidative status was assessed by measurement of peroxides in plasma, and of the thiol redox state in erythrocytes. In addition, endothelial function was assessed by digital reactive hyperemia pulse tonometry using EndoPAT. We observed that the HbNO level was significantly lower in erythrocytes of subjects consuming CPs versus controls (162±8 and 217±12 nmol/L). This correlated with significantly increased levels of plasma peroxides (1.8±0.1mmol/L versus 0.8±0.1mmol/L in controls) and decreased concentrations of erythrocyte reduced thiols (by 12%). Interestingly, the level of oxidized ceruloplasmin-Cu(II) was also significantly higher in the group consuming CPs. The EndoPAT index showed a trend towards impairment in CP users, and was significantly lower in subjects that consumed CPs containing drospirenone, and had lowest erythrocyte HbNO levels. CONCLUSION: This cross-sectional cohort study demonstrates that a decrease of HbNO measured by quantitative EPR in human venous erythrocytes is correlated with the development of endothelial dysfunction under CPs consumption, in parallel with increased vascular oxidative stress.
An increased risk of venous thromboembolism was identified in young women consuming combined contraceptive pills (CP) suggesting a disturbance of vascular homeostasis but the impact of CP on endothelial function and redox status of the vasculature was not thoroughly analyzed. We measured the bioavailability of nitric oxide (NO), a main mediator of vascular homeostasis in a cohort of young female subjects (n=114) and compared the results in users or not of CPs containing ethinyl estradiol and synthetic progestogens. Vascular NO availability was measured by quantification of the heme-nitrosylated hemoglobin (5-coordinate-α-HbNO) concentrations in venous erythrocytes using Electron Paramagnetic Resonance spectroscopy (EPR). Vascular oxidative status was assessed by measurement of peroxides in plasma, and of the thiol redox state in erythrocytes. In addition, endothelial function was assessed by digital reactive hyperemia pulse tonometry using EndoPAT. We observed that the HbNO level was significantly lower in erythrocytes of subjects consuming CPs versus controls (162±8 and 217±12 nmol/L). This correlated with significantly increased levels of plasma peroxides (1.8±0.1mmol/L versus 0.8±0.1mmol/L in controls) and decreased concentrations of erythrocyte reduced thiols (by 12%). Interestingly, the level of oxidized ceruloplasmin-Cu(II) was also significantly higher in the group consuming CPs. The EndoPAT index showed a trend towards impairment in CP users, and was significantly lower in subjects that consumed CPs containing drospirenone, and had lowest erythrocyte HbNO levels. CONCLUSION: This cross-sectional cohort study demonstrates that a decrease of HbNO measured by quantitative EPR in human venous erythrocytes is correlated with the development of endothelial dysfunction under CPs consumption, in parallel with increased vascular oxidative stress.
Authors: Manuel Luque-Ramírez; Andrés E Ortiz-Flores; María Ángeles Martínez-García; María Insenser; Alejandra Quintero-Tobar; Sara De Lope Quiñones; Elena Fernández-Durán; María Lía Nattero-Chávez; Francisco Álvarez-Blasco; Héctor Francisco Escobar-Morreale Journal: J Clin Med Date: 2022-07-03 Impact factor: 4.964
Authors: Irina I Lobysheva; Sandrine van Eeckhoudt; Flavia Dei Zotti; Ahmad Rifahi; Lucie Pothen; Christophe Beauloye; Jean-Luc Balligand Journal: Data Brief Date: 2017-05-12