| Project/Area Number |
06454161
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
General pharmacology
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| Research Institution | KAGAWA MEDICAL SCHOOL |
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Principal Investigator |
ABE Youichi (1995) KAGAWA MEDICAL SCHOOL,PHARMACOLOGY,PROFESSER, 医学部, 教授 (10047227)
安部 陽一 (1994) 香川医科大学, 医学部, 教授
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| Co-Investigator(Kenkyū-buntansha) |
TAMAKI Toshiaki KAGAWA MEDICAL SCHOOL,PHARMACOLOGY,ASSISTANT PROFESSER, 医学部, 助教授 (80179879)
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| Project Period (FY) |
1994 – 1995
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| Project Status |
Completed (Fiscal Year 1995)
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| Budget Amount *help |
¥7,100,000 (Direct Cost: ¥7,100,000)
Fiscal Year 1995: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1994: ¥5,300,000 (Direct Cost: ¥5,300,000)
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| Keywords | Adenosine / Tubuloglomerular feedback / Nitric oxide / Vasopressin / Angiotensin II / Afferent arteriole / Renal hemodynamics / Microdialysis / アデノシンI受容体 |
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| Research Abstract |
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
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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
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