Changes in cardiac oxidative stress, nitric oxide bioavailability, mitochondrial function, and blood pressure in postpartum preeclamptic rats

Background: Preeclampsia (PE) is characterized by new onset hypertension (HTN) during pregnancy that usually occurs in the third trimester and is associated with decreased nitric oxide (NO) bioavailability, increased oxidative stress (OS), and mitochondrial dysfunction. Postpartum (PP) PE women have an increased risk of developing HTN and cardiovascular diseases (CVD) later in life. The timing and mechanisms of this rise in blood pressure (BP) and cardiovascular dysfunction in PP PE women are unknown. Previous studies in our lab indicate that PP PE rats have HTN, increased OS, and cardiac mitochondrial dysfunction at 10 weeks (PP10) (PMID: 34727994). Our current study examines the relationship between BP and cardiac NO bioavailability, OS, and mitochondrial dysfunction at 6 weeks (PP6), an earlier time point from our previous study. We hypothesize that PP6 PE rats will have HTN, increased cardiac OS, decreased cardiac NO bioavailability, and mitochondrial dysfunction.

Methods: Pregnant Sprague Dawley rats were divided into 2 groups: normal pregnant rats (NP) and PE rats, derived from the surgically induced reduced uterine perfusion pressure model of PE (RUPP). All rats gave birth, and their offspring were weaned for 3 weeks. At PP6, BP was measured via carotid catheterization and heart tissues were collected to measure heat shock protein (HSP-1) (a measure of OS), copper zinc superoxide dismutase (CuZnSOD) (an antioxidant), manganese SOD (MnSOD) (a mitochondrial specific antioxidant), endothelial NOS (eNOS) (a measure of NO producing enzyme), and electron transport chain (ETC) proteins (a measure of mitochondrial function). These quantities were obtained through Western blots.

Results: BP was significantly elevated in PP RUPP vs PP NP rats (128±6 vs 106±4mmHg, p < 0.05). HSP-1 was significantly decreased in PP RUPP vs PP NP rats (88±1.51 vs 100±4.05IU/Protein/CON%, p < 0.05). CuZnSOD showed no change between the two groups while MnSOD was drastically increased in PP RUPP vs PP NP (123±2.91 vs 100±5.30IU/Protein/CON%, p < 0.05). eNOS and ETC proteins were unchanged between PP RUPP and PP NP rats.

Conclusion: Contrary to our hypothesis, PP6 PE rats have HTN with no increase in cardiac OS (due to decreased HSP-1 and increased in MnSOD amount) or decrease in cardiac NO bioavailability and mitochondrial dysfunction. These observations are different from our 10-week PP PE rats and may suggest that the heart is protected at 6 weeks PP despite the increase in blood pressure. Future studies will focus on the time frame in which cardiac dysfunction occurs in PP PE rats. Additionally, studies will explore the antioxidant, NO, and mitochondrial pathways along with other cellular mechanisms that may prevent the heart from damage and/or dysfunction after a PE pregnancy. This study is clinically relevant because it will inform clinicians on the mechanisms of HTN and cardiac dysfunction in women following a PE pregnancy as well as provide insights on therapies that could be used to prevent the development of CVDs later in life for PP PE women.