Differential effect of frusemide on renal medullary and cortical blood flow in the anaesthetised rat

In addition to its known effect on renal tubular transport, frusemide (furo semide) has been shown to affect renal circulation. This study in the anaes thetised rat examined the influence of frusemide (bolus 0.25 or 0.5 mg kg(- 1) I.V., then infusion delivering the same dose over 1 h) on renal cortical and medullary circulation measured as laser-Doppler blood (cell) flux. The responses were compared with simultaneously measured changes in renal excr etion and in the tissue admittance, an index of medullary ionic hypertonici ty of the interstitium. Renal vascular responses to frusemide were signific ant but not dose dependent. During low-dose frusemide infusion cortical flu x decreased 11.5 +/- 0.9% and medullary flux decreased 32.3 +/- 3.5% (diffe rence significant at P < 0.001). During high-dose infusion the decreases we re by 13.5 +/- 1.4 and 29.3 +/- 3.8%, respectively (difference significant at P < 0.001). Sodium excretion increased 15-fold (by 3.7 +/- 0.4 mu mol mi n(-1)) and 30-fold (by 5.9 +/- 1.1 mu mol min(-1)) during low- and high-rat e infusion of frusemide, respectively. By contrast, medullary tissue admitt ance decreased similarly with the two doses: maximally by 13.4 +/- 1.4 and 10.9 +/- 0.9%, respectively. The observations that an exaggerated post-frus emide decrease in blood flow within the medulla coincided with decreasing t issue admittance in this zone and that neither medullary blood now nor admi ttance changes were related to the dose suggest a causal relationship betwe en interstitial ionic hypertonicity and vascular resistance. We propose tha t the post-frusemide decrease in medullary tissue NaCl depressed medullary circulation by inhibiting local generation of vasodilator prostaglandins.