Abstract 095: Western Diet consumption in Hyperandrogenemic Females Mediates Exaggerated Hypertension via Increased Oxidative Stress

Background: Polycystic ovary syndrome ( PCOS ) is the major cause of hyperandrogenemia in women. PCOS women are at increased risk of hypertension ( HTN ) and obesity aggravates these risks. Our group previously showed that western diet ( WD ) consumption in a hyperandrogenemic female ( HAF ) rat (model of PCOS) causes exaggerated obesity and HTN. The role of oxidative stress ( OS ) in HTN in males is well-studied, but its role in HTN in PCOS is not clear. This study was designed to test the hypothesis that WD promotes renal OS leading to exaggerated renal injury and HTN in PCOS using a rat model. Methods: Female SD rats (1 month) were implanted with either 5α-dihydrotestosterone (7.5 mg/90 d, s.c.; HAF) or placebo ( CON) pellet, and fed a control diet (CON-CD and HAF-CD groups ( grps )) or WD (CON-WD and HAF-WD grps). At 6 months, urinary proteins, creatinine, albumin and kidney injury molecule ( KIM )-1, renal mitochondrial ( mito. ) complex activities, renal cortical cytosolic superoxide dismutase ( SOD ) and catalase ( CAT ) activities were measured (n=5-7). Mean arterial pressure ( MAP ) at baseline and in response to tempol (SOD mimetic, 30 mg/kg/d, drinking water) was measured by radiotelemetry (7-12 months, new set, n=6-7). Results: Urinary protein and albumin to creatinine ratios were significantly higher in HAF-CD and HAF-WD compared to CON-CD and CON-WD grps (p<0.05). Both ratios were similar between HAF-CD and HAF-WD grps. KIM-1 (marker of proximal tubular injury) was significantly higher only in HAF-WD compared to CON-CD grp (1.4±0.2 vs 0.4±0.1 ng/ml, p<0.05). Renal mito. complex IV activity was higher in HAF-WD compared to HAF-CD (16.1±1.1 vs 7.4±0.2 nmol e - /nmol citrate, p<0.05) and higher in both HAF grps compared to CON-CD and CON-WD grps (p<0.05). Cytosolic SOD activity was lower in HAF-CD and HAF-WD compared to CON-CD and CON-WD grps (1.2±0.1 and 1.0±0.1 vs 1.8±0.2 and 1.7±0.1 U/mg protein, p<0.05). Meanwhile, CAT activity was higher in HAF-WD compared to CON-CD, CON-WD and HAF-CD grps (180±27 vs 100±15, 70±14 and 96±19 nmol/min/mg protein, p<0.05). MAP significantly decreased in HAF-WD with tempol, compared to baseline (116±3 vs 122±1 mmHg, p<0.05). Meanwhile, tempol did not change MAP in CON-CD, CON-WD or HAF-CD grps. Conclusion: Renal cortical OS is exaggerated in HAF-WD with increased proximal tubular injury and a depressor response to tempol. Future studies will determine the potential beneficial effects of mito. targeted therapies on HTN in PCOS.