Brazy P C, Trellis D R, Klotman P E
J Clin Invest. 1985 Nov;76(5):1812-8. doi: 10.1172/JCI112173.
Vasoactive peptides may have direct effects on both renal vasculature and renal tubules. In this study, we examined the direct and immediate effects of bradykinin on oxygen consumption by suspensions of cortical tubules from rabbit kidney. Bradykinin (10(-11) to 10(-7) M) stimulated oxygen consumption rates (QO2) in a dose-dependent manner with a maximal increase of +0.80 +/- 0.13 nmol X mg protein-1 X min-1. This stimulation was prevented by calcium-free media or by the addition of inhibitors of calcium transport, calcium-calmodulin complex formation, Na,K-ATPase activity, mitochondrial respiration, and phospholipase activity. Addition of bradykinin increased the ADP and AMP contents of cortical tubules without changing the ATP content. These data indicate that bradykinin stimulates ATP use and Na,K-ATPase activity. We also examined the effects of exogenous arachidonic acid on QO2 in cortical tubules. Acute additions of arachidonic acid stimulated QO2 at low concentrations (10(-8) to 10(-6) M) and uncoupled mitochondrial respiration at high concentrations (10(-5) M). The effect of arachidonic acid on adenosine nucleotide content was dose-dependent and indicated increased use of ATP. Bradykinin increased QO2 in the presence of low concentrations of arachidonic acid (10(-11) to 10(-9) M), but had no further effect on QO2 in the presence of higher concentrations of arachidonic acid (10(-8) to 10(-6) M). Bradykinin stimulation of QO2 was not prevented by inhibition of cyclooxygenase activity with indomethacin but was prevented by inhibition of lipoxygenase-like activity with nordihydroguariaretic acid. These results suggest that the bradykinin effect on QO2 may be mediated by arachidonic acid release and subsequent metabolism.
血管活性肽可能对肾血管系统和肾小管都有直接作用。在本研究中，我们检测了缓激肽对兔肾皮质肾小管悬液耗氧量的直接和即时作用。缓激肽（10⁻¹¹至10⁻⁷M）以剂量依赖方式刺激耗氧率（QO₂），最大增加量为+0.80±0.13 nmol·mg蛋白⁻¹·min⁻¹。无钙培养基或添加钙转运抑制剂、钙 - 钙调蛋白复合物形成抑制剂、钠钾ATP酶活性抑制剂、线粒体呼吸抑制剂和磷脂酶活性抑制剂可阻止这种刺激。添加缓激肽可增加皮质肾小管的ADP和AMP含量，而不改变ATP含量。这些数据表明缓激肽刺激ATP的利用和钠钾ATP酶活性。我们还检测了外源性花生四烯酸对皮质肾小管QO₂的影响。急性添加花生四烯酸在低浓度（10⁻⁸至10⁻⁶M）时刺激QO₂，在高浓度（10⁻⁵M）时使线粒体呼吸解偶联。花生四烯酸对腺苷核苷酸含量的影响呈剂量依赖性，表明ATP的利用增加。在低浓度花生四烯酸（10⁻¹¹至10⁻⁹M）存在时，缓激肽增加QO₂，但在高浓度花生四烯酸（10⁻⁸至10⁻⁶M）存在时对QO₂没有进一步影响。用吲哚美辛抑制环氧化酶活性并不能阻止缓激肽对QO₂的刺激，但用去甲二氢愈创木酸抑制脂氧合酶样活性可阻止这种刺激。这些结果表明，缓激肽对QO₂的作用可能由花生四烯酸释放及随后的代谢介导。
