Abstract 060: Tauroursodeoxycholic Acid (TUDCA) Prevents High Salt-Induced Renal Damage in ET B Deficient Rats in a Blood Pressure-Independent Manner

• DOI: 10.1161/hyp.68.suppl_1.060
• Publication Date: 2021-06-21T16:51:13Z
• Authors: Carmen De Miguel; Randee Sedaka; Andrew Abad; Janet L Hobbs; David M Pollock; Jennifer S Pollock
• Keywords: Tauroursodeoxycholic acid; Albuminuria

The molecular mechanisms by which the vasoactive peptide endothelin-1 (ET-1) leads to high salt-induced renal damage remain uncertain. These studies were designed determine if ET system induces increasing cellular stress. B deficient (ET def) and transgenic (TG) control rats placed on normal (NSD, 1% NaCl) or salt (HSD, 8% diet for 3 weeks, received daily i.p. injections of stress reliever tauroursodeoxycholic acid (TUDCA, 400 mg/kg/day) vehicle. Blood pressure was monitored telemetry. At end study, inflammation, apoptosis markers kidney assessed. In def rats, HSD significantly increased blood (NSD vs. HSD: 131.2±1.1 153.9±5.9 mmHg, p<0.05), albuminuria, excretion cortical tubular injury KIM-1: 14.2±3.4 104.1±20.6 pg/day; NGAL: 43.6±17.6 215.6±27.7 n=4-7/group; T cell infiltration (5.7±0.3 17.4±4.5 CD3 + cells/field; p<0.05) (4.0±1.0 18.0±4.2 TUNEL+ n=3/group; p<0.05). No changes seen in TG controls HSD. TUDCA treatment prevented HSD-induced as indicated reduced (albumin: 2.3±1.5 ng/day; 55.7±13.8 114.2±18 (10.8±0.5 (1.9±0.3 had no effect medullary pressure. Nephrin remained elevated both genotypes despite treatment. conclusion, loss receptor exaggerated salt-mediated that is attenuated with TUDCA. results highlight protective role receptors against development damage, especially cortex. Funded NIH T32 DK007545 CDM P01 HL95499 HL69999 DMP JSP.