Publication: SGLT2 inhibition potentiates the cardiovascular, renal, and metabolic effects of sGC stimulation in hypertensive rats with prolonged exposure to high-fat diet
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Date
2022-02-01
Authors
Reverte, Virginia ; Rodríguez, Francisca ; Oltra, Lidia ; Moreno, Juan Manuel ; Llinás Más, María Teresa ; Shea, Courtney M ; Schwartzkopf, Chad D. ; Buys, Emmanuel S. ; Masferrer, Jaime L. ; Salazar, Francisco Javier
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Publisher
American Physiological Society
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DOI
https://doi.org/10.1152/ajpheart.00386.2021
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Description
© 2022 The Authors. This manuscript version is made available under the CC-BY 4.0 license http://creativecommons.org/licenses/by/4.0/ This document is the Published Manuscript version of a Published Work that appeared in final form in American Journal of Physiology. Heart and Circulatory Physiology. To access the final edited and published work see https://doi.org/10.1152/ajpheart.00386.2021
Abstract
Prolonged high-fat diet (HFD) accelerates the cardiovascular, renal, and metabolic dysfunction in hypertensive rats with altered renal development (ARDev). Soluble guanylate cyclase (sGC) stimulation or sodium-glucose cotransporter 2 (SGLT2) inhibition may improve cardiovascular, renal, and metabolic function in settings of hypertension and obesity. This study examined whether 6 wk treatment with an SGLT2 inhibitor (empagliflozin, 7 mg/kg/day) enhances the cardiovascular, renal, and metabolic effects of a sGC stimulator (praliciguat, 10 mg/kg/day) in hypertensive rats with ARDev and prolonged exposure to HFD. Arterial pressure (AP), renal vascular resistance (RVR), fat abdominal volume (FAV), insulin resistance, leptin and triglycerides levels, and intrarenal infiltration of inflammatory cells were higher, but cardiac output and creatinine clearance were lower in hypertensive rats (n = 15) than in normotensive rats (n = 7). Praliciguat administration (n = 10) to hypertensive rats reduced (P < 0.05) AP, FAV, plasma concentrations of leptin and triglycerides, and increased (P < 0.05) cardiac output and creatinine clearance. Empagliflozin administration (n = 8) only increased (P < 0.05) glucosuria and creatinine clearance and decreased (P < 0.05) plasma leptin and triglycerides concentrations in hypertensive rats. Simultaneous administration of praliciguat and empagliflozin (n = 10) accelerated the decrease in AP, improved glucose tolerance, reduced (P < 0.05) incremental body weight gain, and decreased (P < 0.05) insulin resistance index, RVR, and the infiltration of T-CD3 lymphocytes in renal cortex and renal medulla. In summary, the combined administration of praliciguat and empagliflozin leads to a greater improvement of the cardiovascular, renal, and metabolic dysfunction secondary to prolonged exposure to HFD in hypertensive rats with ARDev than the treatment with either praliciguat or empagliflozin alone.NEW & NOTEWORTHY This is the first study, to our knowledge, showing that SGLT2 inhibition potentiates the beneficial cardiovascular, renal, and metabolic effects elicited by sGC stimulation in hypertensive rats with prolonged high-fat diet. The effects of the simultaneous administration of praliciguat and empagliflozin are greater than those elicited by either one alone. The effects of the simultaneous treatment may be related to a greater reduction in the inflammatory status.
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Citation
American Journal of Physiology - Heart and Circulatory Physiology, 2022, Vol. 322, Issue 4, pp. H523-H536
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Este ítem está sujeto a una licencia Creative Commons. http://creativecommons.org/licenses/by/4.0/