Renal Oxidative Stress May Explain Sex Differences in Blood Pressure in Adult Offspring Exposed to an Impoverished Environment
Authors: Castillo Angie , Smith Savanna , Jones Kylie , Smith Jonna , Powell Madison , Cunningham Mark 
Published: May 2024

Background: Nearly 40 million people experience poverty in the United States. Poverty is linked to adverse childhood experiences (ACEs) which affects about 64% of adults in the U.S. Previous studies indicate that those who experience ACEs are at a higher risk of developing hypertension (HTN) and cardiovascular diseases (CVDs) later in life, with a greater severity and earlier onset in males. The mechanisms behind the ACEs-attributed development of sex differences in HTN later in life is unknown. One plausible mechanism for this sex difference is increased oxidative stress. One rodent model to mimic poverty as an ACE is the limited bed and nesting (LBN) model. This model simulates an impoverished and low resource environment, as observed in poverty, in which the nesting material during weaning is reduced. We hypothesize that male offspring exposed to LBN will have elevated blood pressure and oxidative stress, while females will have no change in blood pressure and reduced oxidative stress. Methods: Pregnant Sprague Dawley rats gave birth naturally and weaned their offspring for 3 weeks. During the weaning period, on Days 2-9, the dams and their respective pups were divided into 2 groups: LBN and control (CON). After LBN treatment, all rats received normal bedding. After weaning, offspring were divided by sex and experimental status: LBN male (n=5), LBN female (n=5), CON male (n=6), and CON female (n=6). At 16-17 weeks, mean arterial pressure (MAP) was measured via carotid catheterization and the kidneys, brain, heart, and plasma were collected to measure antioxidant capacity via colorimetric biochemical assays. Results: LBN males had a significant increase (18 mmHg) in MAP compared to CON males (128.17±3.93 vs 110.72± 3.93 mmHg, P>0.001), while female LBN and CON rodents displayed no differences. In males, there were no changes in antioxidant capacity in the brain, heart, and plasma. However, there was a significant 2-fold decrease in renal antioxidant capacity (233±14.0 vs 442±12.3 mM Trolox/mg protein, p>0.0001). In females, there were no changes in the kidneys, heart, and brain antioxidant capacity. Conversely, LBN females showed a trending increase in plasma antioxidant capacity compared to CON (3.33±0.16 vs 2.53±0.35 mM Trolox/mg protein, p=0.053). Conclusion: Only males exposed to an impoverished environment during weaning have elevated blood pressure, while females do not. This difference in blood pressure may be explained by decreases in renal antioxidant capacity in males only. On the other hand, females may be protected from elevated blood pressure because they experience a slight increase in systemic antioxidant capacity. Future studies will examine the role of antioxidants in blood pressure regulation in the kidneys. This study is clinically relevant because ACEs affect a large percentage of the American population with about 17% of adults experiencing 4 or more ACEs, with minorities at a greater risk. Understanding the mechanisms on how ACEs contribute to HTN may alleviate some of the racial and ethnic disparities, along with the financial burden on the healthcare system to care for people with HTN and CVDs. Perhaps, organ and sex-specific antioxidant therapies may be used to alter, prevent, or reduce the development of HTN in adults that were exposed to ACEs, such as poverty during nursing and early childhood.

This research was supported by start-up funds and the American Heart Association Early Career Development Award [AHA 18CDA34110264 (Cunningham)].

This is the full abstract presented at the American Physiology Summit 2024 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.