Postpartum preeclamptic rats have hypertension and elevated cerebral oxidative stress




Smith, Savanna
Smith, Jonna
Jones, Kylie
Castillo, Angie
McCafferty, Adair
Wiemann, Natalia
Owen, Malissa
Srivastava, Prakriti
Cunningham, Mark


0000-0001-5949-9799 (Smith, Savanna)

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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 and decreased antioxidant capacity (AC). Our current study examines BP and oxidative stress (OS) in PP PE rats at an earlier time point, 6 weeks (PP6). Understanding changes in cerebral and renal OS may reveal the pathophysiology of HTN, cerebrovascular, and renal disease development in PP PE women. We hypothesize that BP, renal, and cerebral OS 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. Brain and kidney tissues were collected to measure OS (HSP-1, Cu/ZnSOD, and MnSOD proteins and AC) through colorimetric assays and western blots. Results: PP6 PE vs CON rats, BP was elevated (128±6 vs 106±4mmHg, p<0.05) and AC was decreased in systemic circulation (28.5±5.1 vs 36.9±4.5mM Trolox/mg protein, ns). In the brain, both HSP-1 and Cu/ZnSOD were unchanged between PP6 PE and CON rats, while the levels of MnSOD (88.9±2.0 vs 100±2.5 IU/protein/CON %, p<0.05) and AC were decreased (619.1±179.2 vs 850.2±50.3 mM Trolox/mg protein, ns) in PP6 PE vs CON rats. In the kidney, HSP-1 decreased (88.7±3.0 vs 100±4.0 IU/protein/CON %, ns) in PP6 PE vs CON, while Cu/ZnSOD levels remained unchanged. However, kidney MnSOD levels significantly increased (124.3±8.0 vs 100±2.7 IU/protein/CON %, p<0.05) alongside an increase in AC (791.0±165.4 vs 587.0±64.5mM Trolox/mg protein, ns) in PP6 PE vs CON rats. Conclusion: PP6 PE rats have HTN and increased cerebral OS. Despite changes in the brain, kidneys appear to be protected from OS due to a decrease in a reactive OS protein (HSP-1) and increases in antioxidant capacity and protein (MnSOD). Future studies will determine the relationship between brain OS, 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 the maternal health of women after PE pregnancies. In addition, therapy designed to target organ specific OS may be helpful in preventing HTN, cerebrovascular, and chronic kidney diseases later in life for women who have experienced PE.