Mechanism by which dietary protein moduletes renal hemodyr-amies

高蛋白摄入增加肾小球滤过率（GFR）和肾血浆流量。为了阐明其分子机制，我们研究了饲喂低（6%酪蛋白）或高（40%酪蛋白）饲料约8周的大鼠肾小球中类二十烷酸的产生、磷脂酰乙醇胺（PE）特异性磷脂酶A_2 （PLA_2）和环氧化酶的活性以及g蛋白亚基（G_< α >、G_< α i2>、G_< α i3>和G_< β >）的质量。高蛋白喂养的大鼠肾小球比低蛋白喂养的大鼠肾小球产生更多的PGE_2、6-酮PGF_<1alpha>和TxB_2， pe特异性PLA_2和环氧化酶活性增加。与低蛋白饲粮相比，高蛋白饲粮大鼠肾小球G_< α i2>和G_< α i3>减少，肾小球G_< β >增加。同样，这些变化在喂食高蛋白饮食的大鼠中被恢复到与喂食低蛋白饮食的大鼠相当的水平，通过预处理血管紧张素转换酶抑制剂，依那普利拉。此外，最近有报道称G_< β >刺激大鼠心脏PLA_2。综上所述，摄入高蛋白饮食后引起的内源性血管紧张素II水平升高可能激活肾小球G_< β >。高蛋白摄入时肾脏血流动力学的改变可能是由血管扩张性二十烷类化合物、PGE_2和6-酮PGF_< 1α >的作用引起的，这些作用通过激活的G_< β >-诱导的pe特异性pla_2和环氧化酶活性的增加而增强。

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.