1. Mechanisms of SGLT2 (Sodium-Glucose Transporter Type 2) Inhibition-Induced Relaxation in Arteries From Human Visceral Adipose Tissue
- Author
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Nicola Di Daniele, Alessandro De Stefano, Giuseppina Vizioli, Manfredi Tesauro, Carmine Cardillo, and Francesca Schinzari
- Subjects
0301 basic medicine ,medicine.medical_specialty ,Adipose tissue ,Settore MED/09 ,Prostacyclin ,Intra-Abdominal Fat ,030204 cardiovascular system & hematology ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Internal Medicine ,medicine ,Humans ,Hypoglycemic Agents ,Obesity ,Canagliflozin ,Enzyme Inhibitors ,Sodium-Glucose Transporter 2 Inhibitors ,biology ,Liraglutide ,Chemistry ,catalase ,Settore MED/09 - MEDICINA INTERNA ,Glucose transporter ,Vasodilation ,Nitric oxide synthase ,Arterioles ,NG-Nitroarginine Methyl Ester ,030104 developmental biology ,Endocrinology ,biology.protein ,Endothelium, Vascular ,Nitric Oxide Synthase ,Perfusion ,medicine.drug ,Myograph - Abstract
As novel drug treatments for diabetes have shown favorable cardiovascular effects, interest has mounted with regard to their possible vascular actions, particularly in relation to visceral adipose tissue perfusion and remodeling in obesity. The present study tested the vasorelaxing effect of the SGLT2 (sodium-glucose transporter type 2) inhibitor canagliflozin in arteries from visceral adipose tissue of either nonobese or obese humans and investigated the underlying mechanisms. Also, the vasorelaxing effect of canagliflozin and the GLP-1 (glucagon-like peptide 1) agonist liraglutide were compared in arteries from obese patients. To these purposes, small arteries (116–734 μm) isolated from visceral adipose tissue were studied ex vivo in a wire myograph. Canagliflozin elicited a higher concentration-dependent vasorelaxation in arterioles from obese than nonobese individuals ( P =0.02). The vasorelaxing response to canagliflozin was not modified ( P =0.93) by inhibition of nitric oxide synthase (L-NAME) or prostacyclin (indomethacin), or by H 2 O 2 scavenging (catalase); also, canagliflozin-induced relaxation was similar ( P =0.23) in endothelium-intact or -denuded arteries precontracted with high potassium concentration, thereby excluding an involvement of endothelium-derived hyperpolarizing factors. The vasorelaxing response to canagliflozin was similar to that elicited by the Na + /H + exchanger 1 inhibitor BIX ( P =0.67), but greater than that to the Na + /Ca ++ exchanger inhibitor SEA 0400 ( P =0.001), hinting a role of Na + /H + exchanger inhibition in canagliflozin-induced relaxation. In arterioles from obese patients, the vasorelaxing response to canagliflozin was greater than that to liraglutide ( P =0.004). These findings demonstrate that canagliflozin induces endothelium-independent vasorelaxation in arterioles from human visceral adipose tissue, thereby suggesting that SGLT2 inhibition might favorably impact the processes linking visceral adipose burden to vascular disease in obesity.
- Published
- 2021