Vascular and renal responses to stress

描述(由申请人提供)： 项目4的目标是阐明导致变化的机制 在血管和肾功能方面对慢性环境应激和 盐的摄入量很高。项目4将利用Dahl盐敏感(DS)鼠作为 一种对高盐饮食和慢性环境压力敏感的模型。 DS大鼠是一种公认的盐依赖低肾素模型 主要见于非裔美国人的原发性高血压。慢性 环境压力会因反复发生而产生不可预测、不可避免 暴露于空气对头部的高速喷发(空气喷射压力)。目标1 将检验空气喷射压力和高盐饮食的假设 协同提高血压(通过遥测测量)并导致 肠系膜阻力动脉和肠系膜血管的时间和转录变化 肾内髓质。此外，DNA微阵列将识别 在肠系膜阻力动脉和肾脏内部有不同的调节 在这种情况下的延髓。目标2将检验空气喷射器的假设 应激和高盐摄入量通过一种功能障碍来降低血管扩张 一氧化氮合酶。实验将确定空气喷射压力是否 和/或高盐饮食导致肠系膜NO生成减少 阻力动脉和是否增加底物的可用性 对于一氧化氮合酶，L-精氨酸可提高血管扩张能力。 肠系膜动脉。目标3将检验减少的假设 空气喷射应激和高盐摄入期间的血管扩张剂能力是由于 增加了超氧化物的产生。实验将确定喷气式飞机 应激和/或高盐饮食通过以下方式增加超氧化物的产生 血管系统与抗氧化剂是否抑制超氧化物生成 治疗将改善肠系膜动脉的血管扩张能力。目标4 将检验空气喷射压力和高盐摄入量的假设 血管扩张的通过增加血管生成或活性而减少的 内皮素。我们预测慢性空气喷射应激将减少对内皮的依赖。 高盐饮食会加剧血管扩张， 内皮系统的失调是由于功能或功能的丧失 生物可利用的NO通过NO合成酶的失调，增加超氧化物 生产，和/或增加内皮素的生产。我们进一步预测， 在这些慢性环境应激的条件下，NO和ET的平衡， 改变肾脏？S调节动脉压的能力，从一项 DS大鼠血压-钠尿关系的转变。

DESCRIPTION (provided by applicant): The objective of Project 4 is to elucidate mechanisms responsible for changes in vascular and renal function in response to chronic environmental stress and high salt intake. Project 4 will utilize the Dahl salt-sensitive (DS) rat as a model that is sensitive to high salt diet and chronic environmental stress. The DS rat is a well-established model for the salt-dependent low-renin essential hypertension typically found in African Americans. Chronic environmental stress will be produced by recurrent unpredictable, unavoidable exposure to high velocity bursts of air to the head (air jet stress). Aim 1 will test the hypothesis that air jet stress and high salt diet synergistically increase blood pressure (measured by telemetry) and result in temporal and transcriptional changes in mesenteric resistance arteries and renal inner medulla. In addition, DNA micro arrays will identify genes that are differentially regulated in mesenteric resistance arteries and renal inner medulla under these conditions. Aim 2 will test the hypothesis that air jet stress and high salt intake decrease vasodilation through a dysfunction of nitric oxide (NO) synthase. Experiments will determine whether air jet stress and/or high salt diet-induces decreases in the production of NO by mesenteric resistance arteries and whether increasing the availability of the substrate for NO synthase, L-arginine, will improve the vasodilating capacity of the mesenteric arteries. Aim 3 will test the hypothesis that decreased vasodilator capacity during air jet stress and high salt intake is due to increased superoxide production. Experiments will determine whether air jet stress and/or high salt diet increase the production of superoxide by the vasculature and whether inhibiting superoxide production by antioxidant treatment will improve vasodilating capacity of mesenteric arteries. Aim 4 will test the hypothesis that air jet stress and high salt intake mediate a decrease in vasodilation through an increase in the production or activity of endothelin. We predict that chronic air jet stress will reduce endotheliumdependent vasodilation which will be exacerbated by high salt diet and that dysregulation of the endothelial system is through a loss of functional or bioavailable NO via dysregulation of NO synthase, increased superoxide production, and/or increased endothelin production. We further predict that the balance NO and ET, under these conditions of chronic environmental stress, alters the kidney?s ability to regulate arterial pressure as evidenced by a shift in the pressure-natriuresis relationship in the DS rat.