Pharmacological and non pharmacological therapies to prevent NBCe1 impaired activity in ovariectomized cardiomyocytes.

IBAÑEZ AM; GODOY COTO J; YEVES AM; ENNIS IL; LOFEUDO JM; AIELLO EA; DE GIUSTI VC

Congreso; Reunión Anual SAFIS-ALACF 2021 (virtual); 2021

During menopause women are exposed to an increase in cardiovascular risk, typically associated with lack of estrogens. Classic hormone replacement therapy (HRT) has not been as successful as expected in preventing such pathologies, therefore it would be of great importance to describe alternative therapies to prevent cardiovascular risk in menopause. Many of the beneficials effects that estradiol exert on the cardiovascular system are mediated by GPER (G- coupled-estrogen receptor). Sodium/bicarbonate cotransporter (NBC) is an important intracellular pH regulator. Impaired activity of the electrogenic isoform NBCe1 is correlated with increased cardiovascular risk. Objective: explore chronic activation of GPER and aerobic exercise as potential therapies to address intracellular cardiac alterations in OVX hearts. Methods: Bilateral ovariectomy was performed in 10 weeks old female Wistar rats (OVX). The animals were randomly assigned to a sedentary group (OVXsed) or to an aerobic swimming routine (8 weeks/5days a week) (OVXex). Another group of animals underwent a treatment during one month with either G1 (specific agonist of GPER) or vehicle (OVXvh). Data is expressed as mean±SEM, and was analyzed using a one way ANOVA with Tukey postest for multiple comparisons. Results. NBCe1 activity was diminished in OVX and aerobic training was able to prevent it parcially. (Change of pH after activation of NBCe1 with high K+: SHAM 0,249±0,019, n=4; OVXsed 0,090±0,015 n=7*; OVXex 0,144±0,014 n=12) Chronic GPER activation with G1 completely restored NBCe1 activity to sham levels (SHAM 0,149±0,018, n=9; OVXvh 0,065±0,008 n=7*; OVXG1 0,148±0,045 n=4). Conclusion: NBCe1 activity is impaired in OVX cardiac myocytes, and it can be modulated using both pharmacological and non pharmacological therapies. Future experiments will help to further describe the effect of these therapies in cardiac alterations after OVX.