Evidence against a role of arachidonic acid metabolites in autoregulatory responses of the isolated perfused kidney of the rat.

The role of arachidonic acid metabolites in renal autoregulatory responses to changes in pressure was examined in rat isolated perfused kidneys. We also studied the influence of diabetes, a condition associated with hyperfiltration and altered renal eicosanoid production, on autoregulatory responses. The perfused rat kidney demonstrated autoregulation of flow within a pressure range of 100-150 mm Hg, with no differences between diabetic and control rat kidneys. Nifedipine resulted in vasodilatation and loss of autoregulation. Inhibition of the cyclooxygenase pathway of arachidonic acid metabolism with indomethacin failed to alter autoregulatory capacity. Similarly, inhibition of lipoxygenase with BW755C or NDGA, or inhibition of cytochrome P450-dependent enzymes with NDGA, clotrimazole or 7-ethoxyresorufin were without effect on autoregulatory responses. In vivo treatment with stannous chloride to deplete renal cytochrome P450-dependent enzymes also failed to modify autoregulatory responses. These results argue against a role of arachidonic acid metabolites in autoregulation of perfusate flow in the isolated kidney.