RENAL GLOMERULAR HEMODYNAMICS--NEURAL CONTROL MECHANISM

肾小球血流动力学--神经控制机制

• 批准号: 3472575
• 负责人: JOHN T FLEMING
• 金额: $ 9.49万
• 依托单位: UNIVERSITY OF LOUISVILLE
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-04-01 至 1995-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3472575
• 关键词: adrenergic receptor; angiotensin II; calcium channel blockers; calcium flux; glomerular filtration; kidney circulation; laboratory rat; microcirculation; normetanephrine; renal hypertension; vascular resistance; vasoconstriction

The long-term objective of the research is to elucidate the mechanisms which mediate and regulate renal vascular (preglomerular and postglomerular) responses to increase in neural activity. The elucidation of normal control mechanisms will help to identify altered mechanisms in pathological conditions associated with elevated renal nerve activity and loss of kidney function (hypertension). The proposed research will address the following concepts: 1) Increases in renal nerve activity differentially nerve activity , constriction of specific vessels is induced by norepinephrine, alone or in combination with angiotensin II, (3) Different alpha-1 adrenergic receptor subtypes mediate norepinephrine constriction of different renal and (4) Constriction of large arteries versus small arterioles to nerve stimulation is mediated by calcium derived from different sources (extracellular versus intracellular). These concepts will be addressed by observing the in vivo renal microcirculation of the rat hydronephrotic kidney. The diameters of preglomerular vessels, glomerular capsules and capillaries, and efferent arterioles will be measured directly from a calibrated television monitor during direct stimulation of the renal nerve (at varing frequencies or duration) or during reflex-induced increase in renal nerve activity. Stimulation- response curves will be generated for each vascular site to compare relative vessel reactivity. Glomerular hemodynamic changes will be assessed by direct measurements of glomerular capillary pressure (servo- null system)and blood flow (optical doppler RBC velocimeter). To determine the role of norepinephrine to constrict select vessels via specific receptors, stimulation-response curves will repeated after blockade of alpha-la or alpha-1b adrenergic receptors. Similarly, the role of circulating angiotensin II receptor blockade. Shifts in the stimulation responses curves agonist to cause selective constriction. Attenuation of constrictor responses by calcium entry blockers will reflect the dependency of different vessels on influx of extracellular calcium or intracellular calcium release for constriction to nerve stimulation.

研究的长期目标是阐明其机制 它介导和调节肾血管（肾小球前和 肾小球后）对神经活动增加的反应。 澄清 正常控制机制的研究将有助于识别改变的机制 与肾神经活动升高相关的病理状况和 肾功能丧失（高血压）。 拟议的研究将解决 以下概念：1）肾神经活动增加 不同的神经活动，诱导特定血管的收缩 去甲肾上腺素单独或与血管紧张素 II 联合使用，(3) 不同的 α-1 肾上腺素能受体亚型介导去甲肾上腺素 不同肾的收缩和（4）大动脉的收缩 与小动脉相比，神经刺激是由钙衍生的介导的 来自不同来源（细胞外与细胞内）。 这些 将通过观察体内肾脏微循环来解决概念 大鼠肾积水的肾脏。 肾小球前血管的直径， 肾小球囊和毛细血管以及传出小动脉将 在直接测量期间直接从校准的电视监视器测量 刺激肾神经（以不同的频率或持续时间）或 在反射引起的肾神经活动增加期间。 刺激- 将为每个血管部位生成响应曲线以进行比较 相对血管反应性。 肾小球血流动力学变化将 通过直接测量肾小球毛细血管压力（伺服 零系统）和血流量（光学多普勒红细胞测速仪）。 确定 去甲肾上腺素通过特定的收缩选择血管的作用 受体，刺激反应曲线将在阻断后重复 α-1a或α-1b肾上腺素能受体。 同样，角色 循环血管紧张素 II 受体阻断。 刺激的变化 反应曲线激动剂引起选择性收缩。 衰减 钙进入阻滞剂的缩窄反应将反映依赖性 不同血管对细胞外钙或细胞内钙流入的影响 钙释放以收缩神经刺激。