| Budget Amount *help |
¥14,900,000 (Direct Cost: ¥14,900,000)
Fiscal Year 2004: ¥5,700,000 (Direct Cost: ¥5,700,000)
Fiscal Year 2003: ¥9,200,000 (Direct Cost: ¥9,200,000)
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| Research Abstract |
Close relation exists between the kidney function and cardiovascular morbidity/mortality. Inhibition of the renin-angiotensin system (RAS) and/or aldosterone improve outcome of patients with heart failure. It is suggested that in order to achieve cardiorenal protection, high doses of RAS inhibitors must be used. However, because of elevation of serum creatinine or potassium, many patients are often not treated with RAS blockers or high enough doses. This study aimed to clarify mechanisms that relate the kidney and heart. The means to prevent decline in renal function associated with RAS blockade were investigated.
Non-genomic action of aldosterone : We studied a rapid non-genomic action of aldosterone in isolated microperfused rabbit afferent or efferent arterioles. Aldosterone induced vasoconstriction in both arterioles within 5 minutes, and the constriction was stronger in efferent arterioles. The constriction was not blocked with a mineralocorticoid receptor blocker but blocked with
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phospholipase C inhibitors. In addition, removal of the endothelium enhanced the constriction. Our studies suggest that aldosterone causes constriction of glomerular arterioles via nongenomic mechanisms.
Effect of adenosine A1 receptor blocker (AAB) in Dahl salt sensitive rats (SSR) : Adenosine has unique actions in intrarenal hemodynamics. We studied the effect of AAB or furosemide (Fur) alone or in combination on top of enalapril (ENA) on blood pressure, renal function and histology in SSR. Phenotypic changes of mesangial and epithelial cells were also assessed with immunohistochemistry. Compared with vehicle group, urinary protein excretion and serum creatinine levels were lower in the ENA+FK, ENA+Fur and ENA+FK+Fur groups, and survival rate was 27, 71. 80 and 88%, respectively. Phenotypic changes, particularly those in epithelial cells, were least in the last group. We conclude that in SSR combination of FK, ENA and Fur inhibits macrophage infiltration, phenotypic changes in mesangial and epithelial cells, and thereby protects the kidney and improve survival rate. Less
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