Effect of esaxerenone on the onset of aortic endothelial dysfunction and circulating microparticles in type 1 diabetic male mice.

Endothelial dysfunction exacerbates hypertension and other vascular complications in diabetes mellitus (DM). Circulating microparticles (MPs) and extracellular vesicles released in patients with DM have emerged as novel regulators of endothelial dysfunction. The obstruction of mineralocorticoid receptors (MRs) is a potential therapeutic approach to reduce cardiovascular complications. Their impact on the obstruction of MRs on circulating MPs and endothelial dysfunction in DM remains unclear. DM was induced in mice through a single intravenous dose of streptozotocin (STZ; 200 mg/kg). Esaxerenone (ESAX; 3 mg/kg/day), a MR blocker was administered via diet for 8 weeks. In this study, the aortas of the DM group showed the endothelial dysfunction and the administration of ESAX ameliorated the endothelial-dependent responses. Moreover, ESAX influences the impaired endothelial-dependent responses of DM-derived MPs. Interestingly, MP levels increased in DM whereas decreased after ESAX administration. In the aorta, the DM-derived MPs increased the expression of intercellular adhesion molecule-1 (ICAM-1). ESAX inhibited the adhesion of DM-derived MPs. Moreover, the ICAM-1 inhibitor A205804 shows similar effects as ESAX. These results indicate that the release and adhesion properties of MPs can be partially obstructed by ESAX via the ICAM-1 signaling pathway, which clarifies the other functions beyond the anti-hypertensive effects of ESAX.