Benefit of Mineralocorticoid Receptor Antagonism in AKI: Role of Vascular Smooth Muscle Rac1

• DOI: 10.1681/asn.2016040477
• Publication Date: 2017-01-14T03:10:19Z
• Authors: Jonatan Barrera-C...; Gwennan André-Gré...; Aurelie Nguyen di...; Sebastian M. Lechner; Jérôme Cau; Sonia Prince; Peter Kolkhof; Gervaise Loirand; Vincent Sauzeau; Thierry Hauet; Frédéric Jaisser
• Keywords: Male; rac1 GTP-Binding Protein; Swine; Cells; [SDV]Life Sciences [q-bio]; Myocytes, Smooth Muscle; ischemia-reperfusion; Muscle, Smooth, Vascular; Mice; 03 medical and health sciences; vascular; Smooth Muscle; 616; Animals; Aldosterone; Cells, Cultured; Mineralocorticoid Receptor Antagonists; Myocytes; 0303 health sciences; Cultured; Neuropeptides; Acute Kidney Injury; 3. Good health; Oxidative stress; Reperfusion Injury; Muscle; Smooth

AKI is a frequent complication in hospitalized patients. Unfortunately, there no effective pharmacologic approach for treating or preventing AKI. In rodents, mineralocorticoid receptor (MR) antagonism prevents induced by ischemia-reperfusion (IR). We investigated the specific role of vascular MR mediating IR. also assessed protective effect IR-induced Large White pig, model human mice, deficiency smooth muscle cells (SMCs) protected against kidney IR injury. blockade novel nonsteroidal antagonist, finerenone, genetic deletion SMCs associated with weaker oxidative stress production. Moreover, ischemic kidneys had higher levels Rac1-GTP, required NADPH oxidase activation, than sham control kidneys, and Rac1 Furthermore, blunted production Rac1-GTP after Pharmacologic inhibition prevented pig. Altogether, we show that antagonism, gene SMCs, limited renal injury through effects on Rac1-mediated signaling. The benefits pig provide rational basis future clinical trials assessing this patients IR-mediated