Dapagliflozin Mitigates Hypotension in Lipopolysaccharide-Induced Acute Inflammation Independent of Glycemia Level

Author:

Alanazi Wael A.1ORCID,Alharbi Turki1,El-Nagar Doaa M.2,Albogami Abdullah M.1,Alswayyed Mohammed3ORCID

Affiliation:

1. Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia

2. Department of Zoology, College of Science, King Saud University, Riyadh 11451, Saudi Arabia

3. Department of Pathology, College of Medicine, King Saud University, Riyadh 11451, Saudi Arabia

Abstract

Sodium-glucose cotransporter-2 (SGLT2) inhibitors have been suggested to have anti-inflammatory properties in diabetes. The goal of this study was to evaluate the role of the SGLT2 inhibitor dapagliflozin (DAPA) in the attenuation of lipopolysaccharide (LPS)-induced hypotension. Male Wistar albino rats were divided into normal and diabetic groups and received DAPA (1 mg/kg/day) for two weeks followed by a single dose of 10 mg/kg LPS. Blood pressure was recorded throughout the study and the circulatory levels of cytokines were assessed using a multiplex array, while the aortas were harvested for analysis. DAPA attenuated the vasodilation and hypotension caused by LPS. Mean arterial pressure (MAP) was preserved in the normal and diabetic DAPA-treated septic groups (MAP = 83.17 ± 5.27, 98.43 ± 5.57 mmHg) compared to the vehicle-treated septic groups (MAP = 65.60 ± 3.31, 68.21 ± 5.88 mmHg). Most of the cytokines induced by LPS were decreased in the DAPA-treated septic groups. In the aorta, the inducible nitric oxide synthase-derived nitric oxide had lower expression in the DAPA-treated rats. In contrast, the expression of α-smooth muscle actin, a marker of the vessel’s contractile state, was higher in the DAPA-treated rats in comparison with non-treated septic rats. These findings revealed that the protective role of DAPA against LPS-induced hypotension is likely to be glucose-lowering independent, as was observed in the non-diabetic septic group. Taken together, the results show that DAPA has a potential effect in the prevention of the hemodynamic disturbances of sepsis regardless of glycemia levels.

Funder

University Diabetes Centre and Prince Naif bin AbdulAziz Health Research Center

King Saud University Medical City

Publisher

MDPI AG

Subject

Pharmaceutical Science

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