Hypoxic Cardioprotection by New Antihypertensive Compounds in High Salt-Diet Hypertensive Rats: Glucose Transport Participation and Its Possible Pathway
Por:
Hernández-Serda M.A., Alarcón-López A.Y., Vázquez-Valadez V.H., Briseño-Lugo P., Martínez-Soriano P.A., Leguízamo V., Torres N., González-Terán R., Cárdenas-Granados L.A., Sánchez Muñoz F., Rodríguez E., Lerma C., Zúñiga Muñoz A.M., Ángeles E., Carbó R.
Publicada:
1 ene 2024
Resumen:
Hypertension (HP) is a health condition that overloads the heart and increases the risk of heart attack and stroke. In an infarction, the lack of oxygen causes an exclusive use of glycolysis, which becomes a crucial source of ATP for the heart with a higher glucose uptake mediated by glucose transporters (GLUTs). Due to the unpleasant effects of antihypertensives, new drugs need to be researched to treat this disease. This study aimed to evaluate the cardioprotective effect of three novel antihypertensive compounds (LQMs, “Laboratorio de Química Medicinal”) synthesized from Changrolin under hypoxic conditions with the participation of two primary cardiac GLUT1 and GLUT4 using a high-salt diet HP model. The model used a diet with 10% salt to increase arterial blood pressure in Wistar rats. In isolated cardiomyocytes from these rats, glucose uptake was measured during hypoxia, evaluating the participation of GLUTs with or without the animals’ previous treatment with LQM312, 319, and 345 compounds. In silico calculations were performed to understand the affinity of the compounds for the trafficking of GLUTs. Results: Control cells do shift to glucose uptake exclusively in hypoxia (from 1.84 ± 0.09 µg/g/h to 2.67 ± 0.1 µg/g/h). Meanwhile, HP does not change its glucose uptake (from 2.38 ± 0.24 µg/g/h to 2.33 ± 0.26 µg/g/h), which is associated with cardiomyocyte damage. The new compounds lowered the systolic blood pressure (from 149 to 120 mmHg), but only LQM312 and LQM319 improved the metabolic state of hypoxic cardiomyocytes mediated by GLUT1 and GLUT4. In silico studies suggested that Captopril and LQM312 may mimic the interaction with the AMPK ?-subunit. Therefore, these compounds could activate AMPK, promoting the GLUT4 trafficking signaling pathway. These compounds are proposed to be cardioprotective during hypoxia under HP. © 2024 by the authors.
Filiaciones:
Departamento de Ciencias Químicas FES Cuautitlán, UNAM, Av. 1° de Mayo S/N, Santa María las Torres, Campo Uno, Estado de México, Cuautitlán Izcalli, 54740, Mexico
Departamento de Ciencias Biológicas, FES Cuautitlán, UNAM, Santa María las Torres, Av. 1° de Mayo S/NCampo Uno, Estado de México, Cuautitlán Izcalli, 54740, Mexico
QSAR Analytics SA de CV, Estado de México, Tempano 10, Colonia Atlanta, Cuautitlán Izcalli, 54740, Mexico
Laboratorio de Química Medicinal y Teórica, Departamento de Ciencias Químicas, FESC, UNAM, Av. 1° de Mayo, Col. Sta. María las Torres, Estado de México, Cuautitlán Izcalli, 54740, Mexico
Departamento de Inmunología, Instituto Nacional de Cardiología Ignacio Chávez, Juan Badiano #1, Col. Sección XVI, Tlalpan, Ciudad de México, 14080, Mexico
Laboratorio de Medicina Traslacional UNAM-INC, Instituto Nacional de Cardiología Ignacio Chávez, Juan Badiano #1, Col. Sección XVI, Tlalpan, Ciudad de México, 14080, Mexico
Departamento de Biología Molecular, Instituto Nacional de Cardiología Ignacio Chávez, Juan Badiano #1, Col. Sección XVI, Tlalpan, Ciudad de México, 14080, Mexico
Departamento de Biomedicina Cardiovascular, Instituto Nacional de Cardiología Ignacio Chávez, Juan Badiano #1, Col. Sección XVI, Tlalpan, Ciudad de México, 14080, Mexico
gold, All Open Access; Gold Open Access
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