| Project/Area Number |
15590840
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Kidney internal medicine
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| Research Institution | Kinki University (2004)
Tohoku University (2003) |
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Principal Investigator |
ARIMA Shuji Kinki University, School of Medicine, Associate Professor, 医学部, 助教授 (60323010)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2004: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2003: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | afferent and efferent arterioles / glomerular hemodynamics / glomerular capillary pressure / aldosterone / non-genomic / mineralocorticoid receptor / カルシウムチャネル |
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| Research Abstract |
Recent studies provide evidence that aldosterone (Aldo) accelerates hypertension, proteinuria and glomerulosclerosis in animal models of chronic renal failure. Although the underlying mechanisms are not well defined, Aldo may exert these deleterious renal effects by elevating renal vascular resistance (RVR) and glomerular capillary pressure (P_<GC>). To test this possibility, we examined the action. of Aldo on the in vitro microperfused rabbit afferent (Af-) and efferent arterioles (Ef-Arts), crucial vascular segments to the control of glomerular hemodynamics. Aldo caused dose-dependent constriction in both arterioles with a higher sensitivity in Ef-Arts. These constrictions were observed within 10 minutes. In either arteriole, vasoconstrictor action of Aldo was not affected by a mineralocorticoid receptor antagonist spironolactone and was reproduced by membrane-impermeable albumin-conjugated Aldo, suggesting that the vasoconstrictor actions are nongenomic. This notion was further supported by the finding that neither actinomycin D nor cycloheximide had effect on Aldo-induced constriction in either arteriole. The vasoconstrictor action of Aldo on Af-Arts was inhibited by both nifedipine (L-type calcium channel blocker), whereas that on Ef-Arts was inhibited by efonidipine (both L- and T-type calcium channel blocker) but not nifedipine. In addition, disrupting the endothelium or NO synthesis inhibition significantly augmented the vasoconstriction in Af-Arts, demonstrating that endothelium-derived NO modulates vasoconstrictor actions of Aldo. These results demonstrate that Aldo causes nongenomic vasoconstriction via calcium mobilization thorough L- or T-type voltage-dependent calcium channels in Af- or Ef-Arts, respectively. These vasoconstrictor actions on the glomerular microcirculation may play an important role in the pathophysiology and progression of renal diseases by elevating P_<GC> and RVR especially when endothelium functions are impaired.
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