Development of maternal syndrome during pregnancy enhances the severity of post-partum salt-sensitive hypertension and renal damage in the Dahl SS rat
Authors: Dasinger John Henry , Abais-Battad Justine , Cherian-Shaw Mary , Burns Emily , Walton Samuel , Mattson David 
Published: May 2023

Preeclampsia (PE) is a pregnancy-specific disorder that is characterized by hypertension and proteinuria (maternal syndrome). Our group has demonstrated that Dahl salt-sensitive rats maintained on a low salt casein-based diet (SSC) develop maternal syndrome, while Dahl SS rats maintained on a low salt wheat gluten-based diet (SSWG) are protected. Population-based data demonstrated woman that experience a preeclamptic event are at an increased risk for developing hypertension and kidney disease after the pregnancy relative to woman who have a normotensive pregnancy. Since the SSC are susceptible to developing maternal syndrome, we tested the hypothesis that following a single pregnancy SSC rats would exhibit greater salt sensitive hypertension and renal damage relative to SSWG rats in response to a postpartum high salt (HS) challenge. To test this hypothesis SSC and SSWG rats were exposed to a single pregnancy, allowed to deliver naturally and then pups were weaned at 3 weeks. Following a postpartum urinalysis, dams recovered for one week before a two week HS diet challenge. Blood pressure and proteinuria were tracked throughout the study and immune cell infiltration was assessed at the end of the HS challenge. Despite exhibiting comparable baseline MAP measured via telemetry (135±6 vs 126±4mmHg, p>0.05) and urinary protein excretion levels (42.3±5 vs 26.7.1±7 mg/day, p>0.05, n=4-5/group), the SSC rats exhibit significantly elevated postpartum MAP (147±7 vs 131±2 mmHg, p<0.05) and proteinuria (230±40 vs 75±11 mg/day, p<0.05) relative to the SSWG mated rats. Additionally, when these animals were challenged with a postpartum HS diet, the SSC mated rats exhibited an exacerbated response in both MAP (ΔMAP: 22±5 vs 6±3, p<0.05) and proteinuria (300±25 vs 122±20 mg/day, p<0.05) that is accompanied with a significant reduction in creatinine clearance (CC: 0.31±0.08 vs 0.63±0.02 mL/min/g, p<0.05) relative to the SSWG mated rats. These findings are specific to pregnancy in the SSC rats since diet-matched virgin controls only exhibited a slight ΔMAP (SSC Virgin: 10±4mmHg, SSWG Virgin: 9±1mmHg) in response to a HS diet and comparable CC to the SSWG mated rats (SSC Virgin: 0.48±0.07, SSWG Virgin: 0.63±0.06 mL/min/g, p>0.05). These renal damage phenotypes observed in the mated SSC are associated with a two-fold increase in infiltrating immune cells including monocytes/macrophages, T and B cells relative to all other groups. These data suggest the renal demand of an adverse pregnancy that occurs in maternal syndrome is exacerbated with a secondary insult such as a high salt diet. Future studies will investigate the mechanisms behind these pregnancy-induced renal damage phenotypes and how an adverse pregnancy can lead to worsened health outcomes for both mother and offspring. HL157549, HL161231 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.