Abstract 491: Nox4 Inhibition, by GKT 137831, Decreases Obesity-Associated Vascular Dysfunction and Pro-Fibrotic Effects

The pathophysiological role of Nox4 remains elusive and controversial. Even though Nox4 expression is increased in hypertension, diabetes and obesity, some studies demonstrate that Nox4 deficiency predisposes to obesity and insulin resistance. We showed that Nox1/4 inhibition is renoprotective in diabetes. Whether Nox4 influences vascular function and kidney status in obesity associated with mild diabetes is unclear. We hypothesized that Nox4-specific inhibition is protective against obesity-associated vascular and kidney damage. We studied db/m (control) and db/db mice (obese) mice for 16 weeks receiving 1) vehicle; 2) low dose Nox4 inhibitor, GKT137831 (GKT) (20 mg) and 3) high dose GKT (60 mg) for 16 weeks. Body weight increased in db/db (61.8g ± 0.95) versus controls (33.5g ± 0.72, p