Secretion of medullipin I by the kidney involves the cytochrome P-450 enzyme system

To determine whether secretion of medullipin I by the kidney is dependent on the cytochrome P-450 enzyme system in Sprague-Dawley and spontaneously hypertensive rats (SHR).

Isolated kidneys from Sprague-Dawley rats were perfused with 5% human albumin gassed with 95% O2 and 5% CO2 at 185 mmHg. The resultant renal venous effluent was tested in the SHR for medullipin I-type vasodepressor activity. The kidneys were then treated with ketoconazole, and inhibitor of the cytochrome P-450 enzyme system. After rinsing with 50 ml saline, the last 10 ml of which was saved for a control test (see below), the kidneys were reperfused with 50 ml human albumin and the resultant renal venous effluent was tested for vasodepressor activity. One milliliter of the saline rinse was administered to the SHR and the preketoconazole renal venous effluent was administered after 15 min. The medullipin I-type vasodepression occurred. Thus, inhibition of vasodepression after ketoconazole treatment was not due to residual ketoconazole in the post-treatment renal venous effluent.

Treatment of isolated kidneys with ketoconazole prevented secretion of medullipin I which had been induced by 5% human albumin.

The cytochrome P-450 enzyme system is involved in two major metabolic steps of the medullipin system: synthesis of medullipin I by the kidney and conversion of medullipin I to medullipin II by the liver as shown previously.