Renal medullary interstitial infusion of norepinephrine in anesthetized rabbits: methodological considerations.

Abstract
We tested methods for delivery of drugs to the renal medulla of anesthetized rabbits. Outer medullary infusion (OMI) of norepinephrine (300 ng ⋅ kg−1 ⋅ min−1), using acutely or chronically positioned catheters, reduced both cortical (CBF; 15%) and medullary perfusion (MBF; 23–31%). Inner medullary infusion (IMI) did not affect renal hemodynamics, whereas intravenous infusion reduced CBF (15%) without changes in MBF. During OMI of [3H]norepinephrine, much of the radiolabel (∼40% with chronically positioned catheters) spilled over systemically. Nevertheless, autoradiographic analysis showed the concentration of radiolabel was about fourfold greater in the infused medulla than the cortex. In contrast, during IMI, only ∼5% of the infused radiolabel spilled over into the systemic circulation and ∼64% was excreted by the infused kidney. The resultant intrarenal levels of radiolabel were considerably less with IMI compared with OMI. In rabbits, OMI therefore provides a useful method for targeting agents to the renal medulla, but given the considerable systemic spillover with OMI, its utility is probably limited to substances that are rapidly degraded in vivo.