Abstract MP21: Suppression Of Reactive Oxygen Species Protects The Dahl Salt-sensitive Rat From Developing Maternal Syndrome

Abstract

The Dahl Salt-Sensitive (SS) rat maintained on a low salt diet exhibits a differential response to pregnancy; approximately half develop maternal syndrome (hypertension and proteinuria) while the other half are protected. The exact mechanisms of maternal syndrome are unclear, but it is proposed that reactive oxygen species (ROS) are involved. Previous studies from our laboratory demonstrated the importance of NADPH oxidase (NOX) 2-derived ROS produced by immune cells in the development of salt-sensitive hypertension and renal disease. Given the role of NOX2-derived ROS in the Dahl SS rat, we tested the hypothesis that genetic deletion of the p67phox subunit of NOX2 (SS Ncf2-/- ) will result in the protection from developing maternal syndrome. To test this hypothesis, 8 week old female Dahl SS and SS Ncf2-/- were instrumented with radio-telemeters for continuous measurement of mean arterial pressure (MAP). After a recovery period, baseline MAP was measured as well as an overnight urine collection for markers of renal damage before females were mated with males of the same strain and age. Virgin litter-mate controls were run in parallel. As expected, MAP and protein excretion levels were comparable at baseline between virgin and mated SS Ncf2-/- rats. These parameters remained comparable at the late pregnancy time point (108±3 vs 112±1mmHg, 9±3 vs 16±5mg/day, p >0.05). In contrast to the SS preeclamptic pregnancy, the SS Ncf2-/- mated rats are protected from the development of maternal syndrome (141±8 vs 112±1mmHg, p <0.001; and 98±16 vs 16±5mg/day, p <0.001; in the SS vs SS Ncf2-/- , respectively). This protection is accompanied with a significant reduction in uterine artery resistance index which is a marker of impaired blood flow, in the SS Ncf2-/- (0.85±0.03 vs 0.59±0.02, p <0.01). Despite these phenotypic differences, the number of infiltrating immune cells into kidneys or placentas do not differ between these two groups. These results suggest that NOX2-derived ROS contribute to the pathogenesis of maternal syndrome in the Dahl SS rat, and further investigations are necessary to clarify the source of the ROS within key organs such as the kidney and placenta.