Mechanisms of SGLT2 (Sodium-Glucose Transporter Type 2) Inhibition-Induced Relaxation in Arteries From Human Visceral Adipose Tissue.
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 H2O2 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.
['De Stefano|Alessandro|A|', 'Tesauro|Manfredi|M|', 'Di Daniele|Nicola|N|', 'Vizioli|Giuseppina|G|', 'Schinzari|Francesca|F|', 'Cardillo|Carmine|C|']
D001160:Arterioles D000068896:Canagliflozin D004730:Endothelium, Vascular D004791:Enzyme Inhibitors D006801:Humans D007004:Hypoglycemic Agents D050152:Intra-Abdominal Fat D000069450:Liraglutide D019331:NG-Nitroarginine Methyl Ester D019001:Nitric Oxide Synthase D009765:Obesity D000077203:Sodium-Glucose Transporter 2 Inhibitors D014664:Vasodilation
canagliflozin liraglutide arterioles catalase vasodilation