Control of renal hemodynamics -with special reference to tubulo-glomerular feedback-

控制肾脏血流动力学 - 特别参考肾小管-肾小球反馈 -

• 批准号: 06454161
• 负责人: ABE Youichi
• 金额: $ 4.54万
• 依托单位: KAGAWA MEDICAL SCHOOL
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1994
• 资助国家: 日本
• 起止时间: 1994 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06454161/
• 关键词: Adenosine; Tubuloglomerular feedback; Nitric oxide; Vasopressin; Angiotensin II; Afferent arteriole; Renal hemodynamics; Microdialysis; アデノシンI受容体

Renal blood flow remains constant despite wide variations in the perfusion pressure, a phenomenon known as autoregulation. It is now well established that renal autoregulation is mediated by tubuloglomerular feedback (TGF). TGF is a negative feedback system that stabilizes nephronal blood flow, single nephron glomerular filtration rate, and the tubular flow rate. An increase in renal perfusion pressure increases the tubular flow rate via an increase in GFR.The increased tubular flow rate causes an elevation of sodium chloride concentration at the macula densa. This is sensed by the macula densa and results in an increase in the afferent arteriolar resistance. The purpose of the present investigation is determine transmitters that transmit information from the macula densa as a sensor cell to the afferent arteriole as an effector organ. We have focused on an adenosine and nitric oxide (NO) as possible candidates for the transmitter.I.in vivo experiment 1) adenosine : Relationship betwee … More n the renal hemodynamics and the interstitial levels of adenosine was examined in anesthetized dogs. The intrarenal infusion of hypertonic saline resulted in a decrease of renal blood flow (RBF) following a transient increase of RBF and a significant increase of interstitial adenosine concentration. An adenosine 1 receptor antagonist completely blocked the reduction of RBF induced by the hypertonic saline, indicating a role of adenosine for TGF.2) NO : Intrarenal infusion of vasopressin (AVP) resulted in renal vasoconstriction. However, following pretreatment of a V1-antagonist, AVP caused significant vasodilation. This vasodilation disappeared after treatment with the V2-receptor antagonist. Even in the absence of the V2- antagonist, vasodilation was attenuated by intrarenal infusion of L-NNA which is an inhibitor of NO synthetase.II.in vitro experiment : The afferent arterioles were microdissected from the rabbit kidney. Norepinephrine (NE) decreased the lumen diameter of the afferent arteriole in a dose-dependent manner, but angiotensin II (All) even at a high dose did not affect the lumen diameter. However, after treatment with L-NNA,All constricted the afferent arteriole. AVP decreased the lumen diameter of the afferent arteriole and a V1 antagonist inhibited the vasoconstrictor action of AVP.However, AVP increased the lumen diameter of the NE-constricted afferent arteriole pretreated with a V1 antagonist. This vasodilatory effect of AVP was abolished by a V2 antagonist. These findings suggest that adenosine exerts a significant role of TGF and that NO modulates the actions of various vasoactive substances. Less

肾血流保持恒定，尽管灌注压力有很大的变化，这种现象被称为自动调节。现在已经确定肾自身调节是由小管肾小球反馈（TGF）介导的。TGF是一个稳定肾血流、单肾元肾小球滤过率和肾小管流速的负反馈系统。肾灌注压力的增加通过GFR的增加而增加肾小管流速。管状流速的增加引起黄斑致密处氯化钠浓度的升高。这是由黄斑致密感觉到的，并导致传入小动脉阻力的增加。本研究的目的是确定将信息从作为传感细胞的黄斑致密传递到作为效应器官的传入小动脉的递质。我们关注的是腺苷和一氧化氮（NO）作为可能的候选递质。体内实验1)腺苷：与…之间的关系在麻醉狗的肾脏血流动力学和间质腺苷水平的研究。肾内输注高渗生理盐水导致肾血流量（RBF）在短暂增加和间质腺苷浓度显著增加后降低。腺苷1受体拮抗剂完全阻断高渗生理盐水诱导的RBF减少，提示腺苷对tgf的作用。2)NO：肾内输注加压素（AVP）导致肾血管收缩。然而，在使用v1拮抗剂预处理后，AVP引起了明显的血管舒张。这种血管舒张在使用v2受体拮抗剂后消失。即使在没有V2-拮抗剂的情况下，肾内输注NO合成酶抑制剂L-NNA也能减弱血管舒张。ii .体外实验：显微解剖兔肾的传入小动脉。去甲肾上腺素（NE）以剂量依赖的方式降低传入小动脉的管腔直径，但血管紧张素II （All）即使在高剂量下也不影响管腔直径。然而，经L-NNA治疗后，所有传入小动脉收缩。AVP降低传入小动脉的管腔直径，V1拮抗剂抑制AVP的血管收缩作用。然而，AVP增加了经V1拮抗剂预处理的ne收缩的传入小动脉的管腔直径。AVP的这种血管扩张作用被一种V2拮抗剂所消除。这些发现提示腺苷发挥TGF的重要作用，NO调节多种血管活性物质的作用。少

项目成果

Tomoyuki Shiotsu: "Effect of Moderately Increased Intrapelvic Pressure on Renal Tissue Pressure and Vasopressin Release in Rabbits." Hypertension Res.18. 197-202 (1995)

Tomoyuki Shiotsu：“适度增加盆腔内压力对兔子肾组织压力和加压素释放的影响。”

He Hong: "Effects of a synthetic rat adrenomedullin on regional hemodynamics in rats." Eur.J.Pharmacol. 273. 209-214 (1995)

何红：“合成大鼠肾上腺髓质素对大鼠局部血流动力学的影响。”

Yasuharu Aki: "Nitric oxide may participate in V2 vasopressin-receptor-mediated renal vasodilation." J.Cardiovasc.Pharmacol.23. 331-336 (1994)

Yasuharu Aki：“一氧化氮可能参与 V2 加压素受体介导的肾血管舒张。”

Kunisuke Horiuchi: "Luck of the vasodilatory response in skeletal muscle blood vessels of aged spontaneously hypertensive rats." Heart and Vessels. 11 (in press). (1996)

Kunisuke Horiuchi：“老年自发性高血压大鼠骨骼肌血管中血管舒张反应的运气。”

Toshiaki Tamaki: "Vasodilation induced by vasopressin V2 receptor stimulation in afferentarterioles." Kidney Int.(in press). (1996)

Toshiaki Tamaki：“传入小动脉中加压素 V2 受体刺激诱导血管舒张。”