RENAL GLOMERULAR HEMODYNAMICS--NEURAL CONTROL MECHANISM

肾小球血流动力学--神经控制机制

• 批准号: 3472574
• 负责人: JOHN T FLEMING
• 金额: $ 9.04万
• 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/3472574
• 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.

该研究的长期目标是阐明机制 介导和调节肾血管（前胶质细胞和 后跨膜后）对神经活动增加的反应。 阐明 正常的控制机制将有助于确定改变的机制 与肾神经活性升高和 肾功能的丧失（高血压）。 拟议的研究将解决 以下概念：1）肾神经活动增加 神经活性差异，诱导特定血管的收缩 通过去甲肾上腺素，单独或与血管紧张素II结合，（3） 不同的α-1肾上腺素能受体亚型介导去甲肾上腺素 大动脉的不同肾脏和（4）收缩 与小动脉相对于小动脉刺激是由钙得出的 来自不同来源（细胞外与细胞内）。 这些 通过观察体内肾脏微循环来解决概念 大鼠源自肾脏的肾脏。 前血管的直径， 肾小球毛细血管和毛细血管以及传出动脉将是 直接在直接的电视监视器中直接测量 刺激肾神经（在差异频率或持续时间）或 在反射引起的肾神经活性增加。 刺激 将生成每个血管部位的响应曲线以比较 相对容器反应性。 肾小球血流动力学变化将是 通过直接测量肾小球毛细管压力进行评估（伺服 无效系统）和血流（光学多普勒RBC速度计）。 确定 去甲肾上腺素在特异性上收缩精选血管的作用 受体，刺激反应曲线将在阻塞后重复 α-LA或α-1B肾上腺素能受体。 同样， 循环血管紧张素II受体阻滞。 刺激的变化 响应曲线激动剂会导致选择性收缩。 衰减 钙进入阻滞剂的收缩响应将反映依赖关系 不同血管的细胞外钙或细胞内涌入 钙释放，以收缩神经刺激。