Renal Sinus Fat, Hypertension, and Altered Kidney Function

肾窦脂肪、高血压和肾功能改变

基本信息

  • 批准号:
    9769006
  • 负责人:
  • 金额:
    $ 16.44万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2015
  • 资助国家:
    美国
  • 起止时间:
    2015-09-01 至 2020-08-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Increased renal sinus fat (RSF) in humans is associated with hypertension and renal insufficiency. Obese animals have increased RSF that is associated with marked increases in renal interstitial pressures, suggesting a compressive force on the kidneys. This compression may slow flow in the renal tubules and thereby increase sodium reabsorption, especially in the loop of Henle located in the renal medulla. Consistent with this hypothesis is the finding that obesity results in sodium retention due to increased renal sodium reabsorption and compensatory glomerular hyperfiltration. However, the mechanisms responsible for increased sodium reabsorption are not fully understood, especially in humans. Elucidating the mechanisms and site of these pathological changes will provide a rational approach to developing prevention and treatment strategies for obesity-induced hypertension and renal injury. We propose to use novel magnetic resonance (MR) imaging techniques to evaluate RSF and renal medullary oxygenation in 25 obese hypertensive compared to 25 non-obese hypertensive, 25 obese non-hypertensive, and 25 non-obese non-hypertensive humans. Blood Oxygen Level Dependent (BOLD) MR is a non-invasive imaging technique that can detect levels of tissue oxygenation in humans. To assess the relationship between RSF and sodium reabsorption in the renal medulla, we will measure oxygenation in the renal medulla with BOLD imaging before and after furosemide which inhibits loop of Henle sodium chloride reabsorption. We hypothesize that administration of furosemide will result in greater inhibition of renal medullary sodium reabsorption thereby decreasing oxygen consumption and causing greater BOLD signal increases in obese hypertensives with more RSF than in normal weight hypertensives and non-obese non-hypertensives controls. Although obesity-hypertension is associated with activation of the renin-angiotensin-aldosterone and sympathetic nervous systems, it remains unclear if these changes are linked to RSF accumulation. Therefore, we will also evaluate plasma renin and aldosterone levels and urinary catecholamines to determine their relationships to RSF. To accomplish these aims, the principal investigator will work with a multidisciplinary team including leaders in the fields of renal physiology and obesity-hypertension, clinical nephrology, and cardiovascular/renal imaging. This research will provide the investigator with the necessary tools to translate basic pathophysiologic mechanisms into potential prevention and treatment strategies for a complex and prevalent, clinical disorder. The proposed research will also facilitate the development of the investigator as an independent physician scientist and the data derived from these experiments will be used to apply for R01 funding.
描述(由申请人提供):人类肾窦脂肪(RSF)增加与高血压和肾功能不全有关。肥胖动物的RSF增加,与肾间质压力显著增加相关,表明肾脏受到压缩力。这种压迫可能会减慢肾小管中的血流,从而增加钠的重吸收,特别是在位于肾髓质中的Henle袢中。与这一假设相一致的是,肥胖导致钠潴留,这是由于肾功能增加。 钠重吸收和代偿性肾小球超滤。然而,负责增加钠重吸收的机制尚未完全了解,特别是在人类中。阐明这些病理变化的机制和部位,将为肥胖性高血压和肾损害的防治提供一个合理的途径。我们建议使用新的磁共振(MR)成像技术,以评估RSF和肾髓质氧合在25肥胖高血压相比,25非肥胖高血压,25肥胖非高血压和25非肥胖非高血压的人。血氧水平依赖(BOLD)MR是一种非侵入性成像技术,可以检测人体组织的氧合水平。为了评估RSF与肾髓质钠重吸收之间的关系,我们将在呋塞米抑制Henle氯化钠重吸收环之前和之后用BOLD成像测量肾髓质的氧合。我们假设,呋塞米的管理将导致更大的抑制, 肾髓质钠重吸收,从而减少氧消耗,并导致更大的BOLD信号增加肥胖高血压患者与更多的RSF比正常体重高血压患者和非肥胖非高血压对照。虽然肥胖高血压与肾素-血管紧张素-醛固酮和交感神经系统的激活有关,但尚不清楚这些变化是否与RSF积累有关。因此,我们也将评估血浆肾素和醛固酮水平和尿儿茶酚胺,以确定其与RSF的关系。为了实现这些目标,主要研究者将与多学科团队合作,包括肾脏生理学和肥胖高血压,临床肾脏学和心血管/肾脏成像领域的领导者。这项研究将为研究者提供必要的工具,将基本的病理生理机制转化为潜在的预防和治疗策略,用于复杂和流行的临床疾病。拟议的研究还将促进研究者作为独立的医生科学家的发展,从这些实验中获得的数据将用于申请R 01资金。

项目成果

期刊论文数量(5)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Associations of adiponectin and leptin with brain natriuretic peptide in African Americans: the Jackson Heart Study.
非裔美国人脂联素和瘦素与脑钠尿肽的关联:杰克逊心脏研究。
  • DOI:
    10.1097/xce.0000000000000198
  • 发表时间:
    2020
  • 期刊:
  • 影响因子:
    2.3
  • 作者:
    Horbal,StevenR;Hall,MichaelE;Dinh,PaulC;Smiley,Abbas;Musani,SolomonK;Liu,Jiankang;Taylor,HermanA;Fox,ErvinR;Bidulescu,Aurelian
  • 通讯作者:
    Bidulescu,Aurelian
Delayed Time to Peak Velocity Is Useful for Detecting Severe Aortic Stenosis.
  • DOI:
    10.1161/jaha.116.003907
  • 发表时间:
    2016-10-22
  • 期刊:
  • 影响因子:
    5.4
  • 作者:
    Kamimura D;Hans S;Suzuki T;Fox ER;Hall ME;Musani SK;McMullan MR;Little WC
  • 通讯作者:
    Little WC
Increased Proximal Aortic Diameter is Associated With Risk of Cardiovascular Events and All-Cause Mortality in Blacks The Jackson Heart Study.
  • DOI:
    10.1161/jaha.116.005005
  • 发表时间:
    2017-06-21
  • 期刊:
  • 影响因子:
    5.4
  • 作者:
    Kamimura D;Suzuki T;Musani SK;Hall ME;Samdarshi TE;Correa A;Fox ER
  • 通讯作者:
    Fox ER
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Michael Edward Hall其他文献

Michael Edward Hall的其他文献

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{{ truncateString('Michael Edward Hall', 18)}}的其他基金

Renal Sinus Fat, Hypertension, and Altered Kidney Function
肾窦脂肪、高血压和肾功能改变
  • 批准号:
    8821415
  • 财政年份:
    2015
  • 资助金额:
    $ 16.44万
  • 项目类别:

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