Role of L-type Ca 2+ -channels in the vasorelaxing response to finerenone in arteries of human visceral adipose tissue

• Published in: Physiological reports 2024-09, Vol.12 (18), p.e70062
• Main Authors: Schinzari, Francesca, De Stefano, Alessandro, Sica, Giuseppe, Mettimano, Marco, Cardillo, Carmine, Tesauro, Manfredi
• Format: Article
• Language: English
• Subjects: Adult; Arteries - drug effects; Arteries - metabolism; Calcium Channel Blockers - pharmacology; Calcium Channels, L-Type - metabolism; Female; Humans; Intra-Abdominal Fat - blood supply; Intra-Abdominal Fat - drug effects; Intra-Abdominal Fat - metabolism; Male; Middle Aged; Mineralocorticoid Receptor Antagonists - pharmacology; Naphthyridines - pharmacology; Obesity - metabolism; Vasodilation - drug effects
• ISSN: 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 Ca -channel blocker nifedipine, relaxed arteries contracted with the L-type Ca -channel agonist Bay K8644. In conclusion, finerenone relaxes arteries of human visceral AT, likely through antagonism of L-type Ca channels. This finding identifies a novel mechanism by which finerenone may improve AT perfusion, hence protecting against the cardiometabolic complications of obesity.