Project 1.Stress and African American Male Predisposition for Kidney and Cardiometabolic Disease

摘要

ABSTRACT Young hypertensive African American (AA) males have a 10 to 14-fold greater risk for kidney disease than any other hypertensive group. The reason for this striking disparity remains unknown. What is known is that racism significantly contributes to disease risk in AAs. Our preliminary results suggest that the stress hormone system is activated in AA males in association with perceived racism but not in AA females. These findings raise the questions: why do AA males' experiences of racism result in activation of the hypothalamus-pituitary-adrenal axis (HPA) system and how are AA males and females different in their biological response to perceived racism (PR)? This project proposes to investigate these important questions. The conventional conceptual frame for racism and disease suggests that maladaptive coping methods in perception of stress and in response to racism or stress in general can promote the activation of the HPA system while adaptive methods may mititgate the HPA activation. Therefore, we posit that the AA male health disparity may result from use of maladaptive coping methods that leads to activation of the HPA resulting in increased stress hormones aldosterone (ALDO) and cortisol and sympathetic nerve output, both of which promote cardiorenal diseases. ALDO is known to: be elevated in kidney disease; be higher in AAs; and promote kidney injury in the setting of salt-sensitive hypertension by activating the mineralocorticoid receptor (MR) resulting in subsequent inflammation and fibrosis development through RAC 1 pathway signaling. Thus, ALDO is a stress hormone that likely plays a major role in the kidney disease disparity in this vulnerable group. To test our hypothesis we will recruit AA males and females and administer psychosocial surveys to determine their perceived racism and stress levels; their use of maladaptive coping (anger and hostility); their use of adaptive coping (social support); and their levels of ALDO and cortisol. We will determine whether adaptive coping acts to buffer the increase in ALDO and cortisol while maladaptive coping promotes the increase in ALDO and cortisol levels. Furthermore, we will determine if the ALDO and cortisol levels are associated with increased risk for kidney injury in AAs. We also use animal model to confirm that increased ALDO and cortisol can cause kidney damage in the setting of hypertension. The results from this study will be the first to show the underlying pathophysiology (ALDO) link between racism and kidney disease and, consequently, provide new insights that could lead to more precise treatment of AA for hypertension that will prevent the development of kidney disease that is often associated with hypertension.