Improvement of the cardiovascular effect of methyldopa by complexation with Zn(II): synthesis, characterization and mechanism of action

ACTIS DATO, AGUSTIN; MARTINEZ, VALERIA ROMINA; VELEZ RUEDA, JORGE OMAR; PORTIANSKI, ENRIQUE; DE GIUSTI, VERÓNICA; FERRER, EVELINA; WILLIAMS, PATRICIA ANA MARÍA

Puerto Varas

Congreso; PANAM 2023; 2023

Latin American Association of Physiological Sciences (

Introduction: α-methyldopa (MD) is used for managing hypertension during pregnancy. Zinc deprivation has been associated with many diseases.Objectives: The synthesis of a Zn coordination complex [Zn(MD)(OH)(H2O)2].H2O (ZnMD) provide a promising alternative pathway to improve the biological properties of MD.Methods: Fluorescence spectral studies were conducted to examine the binding of complex with bovine serum albumin (BSA). MD, ZnMD, and ZnCl2 were administered to spontaneous hypertensive rats (SHR) rats during 8 weeks and systolic blood pressure (SBP) and echocardiographic parameters were determined (CICUAL Protocol number: T02-02-2023). Ex vivo assays were conducted to evaluate oxidative stress parameters of cardiac tissues, and cross-sectional area (CSA) and collagen levels of left ventricular cardiomyocytes. The expression of NAD(P)H oxidase subunits (gp91phox and p47phox) and Superoxide Dismutase 1 (SOD1) was quantified through western blot analysis.Results: ZnMD exhibited a moderate affinity for binding with BSA, involving Van der Waals forces and hydrogen bonds. Upon treatment in SHR, a reduction in SBP was observed, being ZnMD more effective than MD (122 ± 8.1 mmHg and 145 ± 5.6 mmHg, at 8th week, respectively, n=4). ZnMD prevented myocardial hypertrophy, improved heart function and reduced cardiac fibrosis. In contrast, MD did not show noticeable differences in these parameters. ZnMD regulated negatively the oxidative damage and increased SOD1 expression, while MD did not show significant effect. Conclusion: Both MD and ZnMD have the potential to be transported by albumin. Our findings provide important evidence suggesting that this complex could be a potential therapeutic drug for the treatment of hypertension and cardiac hypertrophy and dysfunction. Acknowledgments: This work was supported by: UNLP [X/871, V720], CONICET [PIP 1999], CICPBA and ANPCyT [PICT-2019-0945] Argentina. AAD and VRM are fellowship holders of CONICET. ELP, VDG, and EGF are research fellows of CONICET and PAMW is research fellow of CICPBA.