| Budget Amount *help |
¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 1999: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1998: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Research Abstract |
Glomerular hemodynamics and tubuloglomerular feedback (TGF) mechanism were evaluated in anesthetized 9-25-week-old spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY).
Micropuncture experiments revealed that the maximal reduction of proximal stop-flow pressure (SEP), an index of intraglomerular pressure (Pgc), induced by loop of Henle perfusion was significantly larger in SHR than in WKY at 9-10 week old (33 vs. 22% of SFP at zero perfusion), indicating the hyperactivity of TGF in SHR. Systemic blood pressure (SBP) was higher, renal vascular resistance (RVR) was greater, and renal plasma flow (RPF) was less in SHR than in WKY. At 14-16 week old, however, the difference of SFP reduction was not observed (28 vs. 28%). SFP at zero perfusion was comparable among 9-10, 14-16, and 23-25-week-old SHR. Adenosine A1 receptor antagonist (FK838, I.v.) suppressed TGF and increased SFP at zero perfusion in SHR, thus induced an upwards shift of the TGF curve. FK838 increased GFR, RPF, and FENa, while SBP remained unaltered. Adrenomedullin (I.v.) suppressed TGF in SHR to the level in WKY ; the SFP at zero perfusion was unchanged and the tubular flow rate at the steady state increased, indicating a rightwards shift of the TGF curve. SBP and RVR were decreased, GFR unchanged, and RPF and FENa increased by adrenomedullin.
In conclusion, TGF is activated in SHR at 9-10 week old, and Pgc remains normal in 9-25-week-old SHR. A1 antagonist or adrenomedullin suppresses TGF. The former induces the glomerular hypertension and hyperfiltration through the afferent arteriolar vasodilatation. The latter, however, keeps Pgc normal through both afferent and efferent vasodilatation. Adrenomedullin normalizes TGF, induces natriuresis, and lowers SBP, and thereby may prevent the initiation and/or the progression of the glomerular sclerosis in SHR.
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