Postpartum preeclamptic rats have hypertension, elevated cerebral oxidative stress, and inflammation
Authors: Smith Savanna , Smith Jonna , Jones Kylie , Castillo Angie , McCafferty Adair , Wiemann Natalia , Owen Malissa , Srivastava Prakriti , Cunningham Mark 
Published: May 2023

Background: Postpartum (PP) preeclamptic (PE) women have an increased risk for developing hypertension (HTN), cerebrovascular diseases, and chronic kidney diseases later in life. The timing and mechanisms that contribute to a rise in blood pressure (BP), cerebrovascular and kidney dysfunction in PP PE women is unknown and the focus of this study. Previous studies in our lab (PMID: 34727994) indicate PP PE rats at 10 weeks have HTN, decreased antioxidant capacity (AC), and increased inflammation. Our current study examines BP, oxidative stress (OS), and inflammation in PP PE rats at an earlier time point, 6 weeks (PP6). Understanding changes in cerebral and renal OS and inflammation may reveal the pathophysiology of HTN, cerebrovascular, and renal disease development in PP PE women. We hypothesize that BP, renal and cerebral OS and inflammation will increase in PP6 PE rats. Methods: Pregnant Sprague Dawley rats were divided into 2 groups: control (CON) normal pregnant rats, and PE rats, derived from the surgically induced placental ischemic (reduced uterine perfusion pressure) model of PE. All rats gave birth and weaned for 3 weeks. At PP6, BP was measured via carotid catheterization; tissues were collected to measure OS (H2O2 and AC) and inflammation via BCAs and ELISAs. Results: BP was elevated in PP6 PE vs CON rats (128±6 vs 106±4mmHg, p<0.05). AC was decreased in the systemic circulation (28.5±5.1 vs 36.9±4.5mM Trolox/mg protein, ns) and the brain (619.1±179.2[MC1] vs 850.2±50.3 mM Trolox/mg protein, ns) of PP6 PE vs CON rats. However, renal AC was increased in PP6 PE vs CON rats (791±165.4 vs 587±64.5mM Trolox/mg protein, ns). Brain and kidney H2O2 levels were unchanged. However, there was a significant decrease in systemic H2O2 in PP6 PE vs CON rats (9.6±0.21 vs 11.1±0.56nM, p<0.05). Brain IL-17 (331.2±41.1 vs 297.6±48.6pg/mL, ns) and IL-4 (178.4±23.4 vs 154.8±14pg/mL, ns) were increased in PP6 PE vs CON rats, while brain TNF-α drastically increased by ~2.4-fold (2576±445.6 vs 1058±212.5pg/mL, ns) in PP6 PE vs CON rats. Kidney IL-17 displayed a 2-fold decrease in PP6 PE vs CON rats (192.8±28.2 vs 351.4±32.5pg/mL, p<0.02). Conclusion: PP6 PE rats have HTN and increased cerebral OS and inflammation. Despite changes in the brain, kidneys appear to be protected. Future studies will determine the relationship between brain OS and inflammation, HTN, and cerebral damage/dysfunction to PP PE rats. Furthermore, future studies will be designed to elucidate the protective mechanisms of the kidney in PP6 PE rats. Findings of this study are clinically relevant and could be used to improve maternal health following a PE pregnancy in terms of timing and targeting specific factors (OS and inflammation) that cause HTN, cerebrovascular, and chronic kidney diseases later in life.

This research was supported by the American Heart Association Early Career Development Award [AHA 18CDA34110264 (Cunningham)]

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.