Secretion of medullipin I by the kidney requires oxygen

ObjectiveTo test the hypothesis that the secretion of medullipin I by the kidney involves an oxidative step.DesignMedullipin I is secreted by kidney renomedullary interstitial cells and is converted to medullipin II by the liver. Medullipin I can be derived from the kidney in the renal venous effluent by perfusing normal rat kidneys with 95% O2--5% CO2 at an elevated pressure (180 mmHg). To evaluate whether the secretion of medullipin I involves an oxidative step normal rat kidneys were perfused at an elevated pressure in the presence of O2, in the absence of O2 and after treatment of the kidneys with a powerful antioxidant.MethodsNormal rat kidneys were perfused with 5% albumin bubbled with O2-CO2 at 180 mm Hg. This was the control procedure for each of the three approaches. In approach (1), the kidneys were perfused with 5% albumin bubbled with N2. In approach (2), the kidneys were perfused with 'blood' treated with carbon monoxide. In approach (3), the kidneys were treated with the antioxidant butylated hydroxytoluene then perfused with 5% albumin bubbled with O2-CO2. Each perfusate was tested for medullin I activity by rapid intravenous injection into the SHR.ResultsAll three approaches, which exclude the action of molecular O2, prevented the secretion of medullin I by the kidneys.ConclusionThe secretion of medullin I by the kidneys involves an oxidative step.