| Budget Amount *help |
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1992: ¥300,000 (Direct Cost: ¥300,000)
Fiscal Year 1991: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Research Abstract |
High protein intake increases glomerular filtration rate (GFR) and renal plasma flow. To elucidate the molecular mechanisms, we examined the production of eicosanoids, the activities of phosphatidylethanolamine (PE)-specific phospholipase A_2 (PLA_2) and cyclooxygenase and the mass of G-protein subunits (G_<alphas>, G_<alphai2>, G_<alphai3>, and G_<beta>) in glomeruli isolated from rats fed a low (6% casein) or high (40% casein) protein diet for approximately 8 weeks. Glomeruli isolated from high protein-fed rats produced significantly greater amounts of PGE_2, 6-keto PGF_<1alpha>, and TxB_2 than glomeruli isolated from low protein-fed rats with increased activities of PE-specific PLA_2 and cyclooxygenase. Compared to rats fed a low protein diet a decrement in glomerular G_<alphai2> and G_<alphai3> and an increment in glomerular G_<beta> were observed in rats fed a high protein diet. Also these changes seen in rats fed a high protein diet were restored to the levels comparable to those observed in rats fed a low protein diet by pretreating the rats with the angiotensin converting enzyme inhibitor, enalaprilat. Moreover, it has been recently reported that G_<beta> stimulates PLA_2 in rat heart. In conclusion, elevated levels of endogenous angiotensin II induced after ingestion of a high protein diet may activate glomerular G_<beta>. Changes in renal hemodynamics observed in high protein intake may be caused by the action of vasodilatory eicosanoids, PGE_2 and 6-keto PGF_<1alpha>, which are augmented via the activated G_<beta>-induced increases in the activities of PE-specific-PLA_2 and cyclooxygenase.
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