Bradykinin stimulation of oxidative metabolism in renal cortical tubules from rabbit. Possible role of arachidonic acid.

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Abstract

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.

Authors

P C Brazy, D R Trellis, P E Klotman