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Dapagliflozin has No Protective Effect on Experimental Pulmonary Arterial Hypertension and Pulmonary Trunk Banding Rat Models

Sodium-glucose cotransporter-2 (SGLT2) inhibitors, a novel class of hypoglycemic drugs, show excellent cardiovascular benefits, and have further improved heart failure outcomes, significantly reducing cardiovascular and all-cause mortality irrespective of diabetes status. However, the efficacy of SG...

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Autores principales: Li, Huayang, Zhang, Yitao, Wang, Shunjun, Yue, Yuan, Liu, Quan, Huang, Suiqing, Peng, Huajing, Zhang, Yi, Zeng, Weijie, Wu, Zhongkai
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8591217/
https://www.ncbi.nlm.nih.gov/pubmed/34790128
http://dx.doi.org/10.3389/fphar.2021.756226
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author Li, Huayang
Zhang, Yitao
Wang, Shunjun
Yue, Yuan
Liu, Quan
Huang, Suiqing
Peng, Huajing
Zhang, Yi
Zeng, Weijie
Wu, Zhongkai
author_facet Li, Huayang
Zhang, Yitao
Wang, Shunjun
Yue, Yuan
Liu, Quan
Huang, Suiqing
Peng, Huajing
Zhang, Yi
Zeng, Weijie
Wu, Zhongkai
author_sort Li, Huayang
collection PubMed
description Sodium-glucose cotransporter-2 (SGLT2) inhibitors, a novel class of hypoglycemic drugs, show excellent cardiovascular benefits, and have further improved heart failure outcomes, significantly reducing cardiovascular and all-cause mortality irrespective of diabetes status. However, the efficacy of SGLT2 inhibitors in pulmonary arterial hypertension (PAH) and right ventricular (RV) dysfunction remains unknown. This study aimed to evaluate the effects of dapagliflozin in rats with PAH and RV dysfunction. PAH was induced in rats by monocrotaline (MCT) subcutaneous injection (60 mg/kg). Isolated RV dysfunction was induced in another group of rats by pulmonary trunk banding (PTB). Dapagliflozin (1.5 mg/kg) was administered daily via oral gavage one day (prevention groups) or two weeks (reversal groups) after modeling. Echocardiography and hemodynamic assessments were used to observe pulmonary vascular resistance and RV function. Histological staining was used to observe pulmonary vascular and RV remodeling. As compared with MCT group, dapagliflozin treatment did not significantly improve the survival of rats. Pulmonary arterial media wall thickness in MCT group was significantly increased, but dapagliflozin did not significantly improved vascular remodeling both in the prevention group and reversal group. In MCT group, RV hypertrophy index, RV area, the fibrosis of RV increased significantly, and RV function decreased significantly. Consistently, dapagliflozin did not show protective effect on the RV remodeling and function. In the PTB model, we also did not find the direct effect of dapagliflozin on the RV. This is a negative therapeutic experiment, suggesting human trials with dapagliflozin for PAH or RV failure should be cautious.
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spelling pubmed-85912172021-11-16 Dapagliflozin has No Protective Effect on Experimental Pulmonary Arterial Hypertension and Pulmonary Trunk Banding Rat Models Li, Huayang Zhang, Yitao Wang, Shunjun Yue, Yuan Liu, Quan Huang, Suiqing Peng, Huajing Zhang, Yi Zeng, Weijie Wu, Zhongkai Front Pharmacol Pharmacology Sodium-glucose cotransporter-2 (SGLT2) inhibitors, a novel class of hypoglycemic drugs, show excellent cardiovascular benefits, and have further improved heart failure outcomes, significantly reducing cardiovascular and all-cause mortality irrespective of diabetes status. However, the efficacy of SGLT2 inhibitors in pulmonary arterial hypertension (PAH) and right ventricular (RV) dysfunction remains unknown. This study aimed to evaluate the effects of dapagliflozin in rats with PAH and RV dysfunction. PAH was induced in rats by monocrotaline (MCT) subcutaneous injection (60 mg/kg). Isolated RV dysfunction was induced in another group of rats by pulmonary trunk banding (PTB). Dapagliflozin (1.5 mg/kg) was administered daily via oral gavage one day (prevention groups) or two weeks (reversal groups) after modeling. Echocardiography and hemodynamic assessments were used to observe pulmonary vascular resistance and RV function. Histological staining was used to observe pulmonary vascular and RV remodeling. As compared with MCT group, dapagliflozin treatment did not significantly improve the survival of rats. Pulmonary arterial media wall thickness in MCT group was significantly increased, but dapagliflozin did not significantly improved vascular remodeling both in the prevention group and reversal group. In MCT group, RV hypertrophy index, RV area, the fibrosis of RV increased significantly, and RV function decreased significantly. Consistently, dapagliflozin did not show protective effect on the RV remodeling and function. In the PTB model, we also did not find the direct effect of dapagliflozin on the RV. This is a negative therapeutic experiment, suggesting human trials with dapagliflozin for PAH or RV failure should be cautious. Frontiers Media S.A. 2021-11-01 /pmc/articles/PMC8591217/ /pubmed/34790128 http://dx.doi.org/10.3389/fphar.2021.756226 Text en Copyright © 2021 Li, Zhang, Wang, Yue, Liu, Huang, Peng, Zhang, Zeng and Wu. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Li, Huayang
Zhang, Yitao
Wang, Shunjun
Yue, Yuan
Liu, Quan
Huang, Suiqing
Peng, Huajing
Zhang, Yi
Zeng, Weijie
Wu, Zhongkai
Dapagliflozin has No Protective Effect on Experimental Pulmonary Arterial Hypertension and Pulmonary Trunk Banding Rat Models
title Dapagliflozin has No Protective Effect on Experimental Pulmonary Arterial Hypertension and Pulmonary Trunk Banding Rat Models
title_full Dapagliflozin has No Protective Effect on Experimental Pulmonary Arterial Hypertension and Pulmonary Trunk Banding Rat Models
title_fullStr Dapagliflozin has No Protective Effect on Experimental Pulmonary Arterial Hypertension and Pulmonary Trunk Banding Rat Models
title_full_unstemmed Dapagliflozin has No Protective Effect on Experimental Pulmonary Arterial Hypertension and Pulmonary Trunk Banding Rat Models
title_short Dapagliflozin has No Protective Effect on Experimental Pulmonary Arterial Hypertension and Pulmonary Trunk Banding Rat Models
title_sort dapagliflozin has no protective effect on experimental pulmonary arterial hypertension and pulmonary trunk banding rat models
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8591217/
https://www.ncbi.nlm.nih.gov/pubmed/34790128
http://dx.doi.org/10.3389/fphar.2021.756226
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