Neurohumoral control of arteries and veins in obesity-associated hypertension

肥胖相关高血压中动脉和静脉的神经体液控制

• 批准号: 9253084
• 负责人: Gregory D Fink
• 金额: $ 136.88万
• 依托单位: MICHIGAN STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-07-10 至 2020-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9253084
• 关键词: Address; Adipose tissue; Adrenergic Agents; Adult; Affect; Age; Animals; Arteries; Blood; Blood Circulation; Blood Pressure; Blood Vessels; Blood Volume; Blood flow; Cardiac Output; Cardiovascular Diseases; Cardiovascular system; Catecholamines; Cessation of life; Characteristics; Child; Chronic; Clinical; Clinical Management; Conscious; Disease; Electric Capacitance; Excess Mortality; Fatty acid glycerol esters; Functional disorder; Goals; Health; Heart; High Fat Diet; High Prevalence; Hormonal; Human; Hyperphagia; Hypertension; In Vitro; Infiltration; Inflammation; Kidney; Lead; Link; Literature; Measurement; Mediator of activation protein; Mesentery; Mineralocorticoids; Modeling; Molecular; Morbidity - disease rate; Nerve; Neuroeffector Junction; Norepinephrine; Obesity; Obesity Related Hypertension; Organ; Overweight; Patients; Peripheral; Physiological; Rattus; Regulation; Research; Resistance; Risk Factors; Rodent; Rodent Model; Role; Seminal; Source; Sympathetic Nervous System; System; Techniques; Testing; Thinness; Tissues; United States; Vascular Capacitance; Veins; Venous; Visceral; Work; afferent nerve; base; blood pressure regulation; constriction; cytokine; disability; experimental study; feeding; improved; in vivo; instrument; macrophage; mortality; neuromechanism; neurotransmission; novel; novel strategies; premature; pressure; programs; public health relevance; response; salt sensitive hypertension; transmission process

DESCRIPTION (provided by applicant): Overall Hypertension is a major risk factor for premature death and disability in the United States. New approaches to therapy are needed to improve clinical management and reduce mortality and morbidity. Our Program Project is based on the assumption that redistribution of peripherally stored blood toward the heart via changes in vascular capacitance is an important factor in the pathophysiology of hypertension. Since most peripherally stored blood is in the splanchnic veins, redistribution is driven largely by reduced splanchnic venous capacitance. This can be caused by active constriction of splanchnic arteries, or active or passive constriction of splanchnic veins. Over the past five years our Program Project has focused on characterizing sympathetic neural mechanisms that regulate venous capacitance, with emphasis on differential control of arterial and venous function. Most of our work has been conducted in rodents with mineralocorticoid-salt hypertension. However, clinical hypertension is increasingly associated with obesity and especially with accumulation of inflamed visceral fat in the splanchnic region. Combined with evidence of sympathetic overactivity in obesity, this led us to hypothesize that altered sympathetic control of splanchnic arteries and veins could be a critical link between obesity and hypertension. Therefore, recently we have begun to refocus our work on a high fat feeding model of obesity-related hypertension in rodents and on complementary studies in splanchnic blood vessels and fat obtained from human patients. Over the next five years we propose to: 1) perform in vivo physiological studies in our rodent model to determine the amount, source and impact on arterial pressure of splanchnic sympathetic drive in obesity-related hypertension; 2) examine in rat and human blood vessels how inflamed visceral fat impacts sympathetic neurotransmission; and 3) establish in rat and human blood vessels the importance of both a) sympathetic drive to perivascular adipose tissue and b) a newly discovered adrenergic system endogenous to perivascular adipose tissue itself.

描述（由申请人提供）：总体而言，高血压是美国过早死亡和残疾的主要危险因素。需要新的治疗方法来改善临床管理并降低死亡率和发病率。我们的项目基于这样的假设：通过血管容量的变化将外周储存的血液重新分配到心脏是高血压病理生理学的一个重要因素。由于大多数外周储存的血液在内脏静脉中，因此重新分布主要是由内脏静脉电容减少驱动的。这可能是由内脏动脉主动收缩或内脏静脉主动或被动收缩引起的。在过去的五年中，我们的项目重点关注调节静脉电容的交感神经机制，重点是动脉和静脉功能的差异控制。我们的大部分工作都是在患有盐皮质激素盐高血压的啮齿动物身上进行的。然而，临床高血压越来越多地与肥胖相关，尤其是与内脏区域发炎的内脏脂肪堆积相关。结合肥胖症中交感神经过度活跃的证据，这使我们推测内脏动脉和静脉的交感神经控制改变可能是肥胖和高血压之间的关键联系。因此，最近我们开始将工作重点重新集中在啮齿类动物肥胖相关高血压的高脂肪喂养模型上，以及从人类患者身上获得的内脏血管和脂肪的补充研究上。在接下来的五年里，我们建议：1）在我们的啮齿动物模型中进行体内生理研究，以确定肥胖相关高血压中内脏交感神经驱动的数量、来源和对动脉压的影响； 2) 在大鼠和人类血管中检查发炎的内脏脂肪如何影响交感神经传递； 3）在大鼠和人类血管中确定a）对血管周围脂肪组织的交感神经驱动和b）新发现的血管周围脂肪组织本身内源性肾上腺素能系统的重要性。