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

摘要 年轻的高血压非洲裔美国人（AA）男性患肾脏疾病的风险比任何人高10至14倍。 其他高血压组。造成这一显著差异的原因尚不清楚。众所周知，种族主义 显著增加了AA的疾病风险。我们的初步结果表明，应激激素系统 在AA男性中激活，与感知的种族主义有关，但在AA女性中没有。这些发现提高了 问题：为什么AA男性的种族主义经历会导致下丘脑-垂体-肾上腺的激活 轴（HPA）系统，以及AA男性和女性在对感知的生物反应方面有何不同 种族主义（PR）？本项目旨在研究这些重要问题。传统概念 种族主义和疾病的框架表明，在压力感知和心理健康方面， 对种族主义或压力的反应一般可以促进HPA系统的激活，而适应性方法 可以减轻HPA激活。因此，我们认为AA男性健康差异可能是由于使用 适应不良的应对方法，导致HPA激活，导致应激激素增加 醛固酮（ALDO）和皮质醇以及交感神经输出，这两者都促进心肾疾病。 已知ALDO：在肾脏疾病中升高;在AA中较高;并在以下情况下促进肾损伤： 盐敏感性高血压通过激活盐皮质激素受体（MR）导致随后的 炎症和纤维化发展通过RAC 1途径信号传导。因此，ALDO是一种应激激素 这可能在这一弱势群体的肾脏疾病差异中发挥了重要作用。为了验证我们的假设， 将招募AA男性和女性，并进行心理社会调查，以确定他们认为的种族主义 和压力水平;他们使用适应不良的应对（愤怒和敌意）;他们使用适应性应对（社会 支持）;和他们的ALDO和皮质醇水平。我们将确定适应性应对是否起到缓冲作用， 适应不良的应对方式促进了ALDO和皮质醇水平的增加。 此外，我们将确定ALDO和皮质醇水平是否与肾脏疾病风险增加相关。 受伤的AAs我们还用动物模型证实了ALDO和皮质醇的升高可引起肾脏 在高血压的背景下损害。这项研究的结果将首次揭示 病理生理学（ALDO）的种族主义和肾脏疾病之间的联系，因此，提供了新的见解， 可能导致更精确的治疗AA的高血压，将防止肾脏的发展， 常与高血压有关的疾病。

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.