Role of L‐type Ca2+‐channels in the vasorelaxing response to finerenone in arteries of human visceral adipose tissue

• Published in: Physiological reports Vol. 12; no. 18; pp. e70062 - n/a
• Main Authors: Schinzari, Francesca, De Stefano, Alessandro, Sica, Giuseppe, Mettimano, Marco, Cardillo, Carmine, Tesauro, Manfredi
• Format: Journal Article
• Language: English
• Published: Oxford John Wiley & Sons, Inc 01.09.2024; John Wiley and Sons Inc; Wiley
• Subjects: Adipose tissue; Arteries; Biopsy; Body fat; Body mass index; Calcium (blood); Calcium channels; Diabetes; Dihydropyridine; Endothelium; finerenone; Gastrointestinal surgery; Immunohistochemistry; Insulin resistance; Kidney diseases; mineralocorticoid receptor; Mineralocorticoid receptors; Nifedipine; Nitric oxide; Nitric-oxide synthase; Obesity; Oxidative stress; Potassium; Short Report; Vasoactive agents; Veins & arteries; Italy; St Louis Missouri; United Kingdom > UK; United States > US
• ISSN: 2051-817X; 2051-817X
• DOI: 10.14814/phy2.70062

Inadequate blood supply to the expanding adipose tissue (AT) is involved in the unhealthy AT remodeling and cardiometabolic consequences of obesity. Because of the pathophysiological role of upregulated mineralocorticoid receptor (MR) signaling in the complications of obesity, this study tested the vasoactive properties of finerenone, a nonsteroidal MR antagonist, in arteries of human AT. Arteries isolated from the visceral AT of obese subjects were studied in a wire myograph. Finerenone resulted in a concentration‐dependent relaxation of arteries precontracted with either the thromboxane‐A2 analog U46619, ET‐1, or high‐K+ solution; the steroidal MR antagonist potassium canrenoate, by contrast, did not relax arteries contracted with either U46619 or high‐K+ solution. Finerenone‐induced relaxation after precontraction with U46619 was greater in the arteries of obese versus nonobese subjects. Mechanistically, the vasorelaxing response to finerenone was not influenced by preincubation with the nitric oxide synthase inhibitor L‐NAME or by endothelium removal. Interestingly, finerenone, like the dihydropyridine Ca2+‐channel blocker nifedipine, relaxed arteries contracted with the L‐type Ca2+‐channel agonist Bay K8644. In conclusion, finerenone relaxes arteries of human visceral AT, likely through antagonism of L‐type Ca2+ channels. This finding identifies a novel mechanism by which finerenone may improve AT perfusion, hence protecting against the cardiometabolic complications of obesity. The vasoactive response to the nonsteroidal mineralocorticoid receptor antagonist (MRA) finerenone was tested ex vivo in arteries of human visceral adipose tissue (VAT). Finerenone elicited endothelium‐independent vasorelaxation in arteries precontracted with different vasoconstrictors; the steroidal MRA potassium canrenoate, by contrast, did not relax those arteries. Both finerenone and the L‐type calcium channels (LTCCs) antagonist nifedipine relaxed arteries contracted with the LTCCs agonist BAY K8644. These findings suggest that blockade of LTTCs, rather than antagonism of the mineralocorticoid receptor, is the likely mechanism of the finerenone‐induced relaxation in human VAT arteries.