Effect of bumetanide, frusemide and prostaglandin E2 on the isolated perfused kidney of rat and rabbit.

Rat and rabbit kidneys were isolated, perfused via the renal artery with Krebs solution and perfusion pressure monitored. Dose-response curves to noradrenaline administered as bolus doses or frequency-response curves from transmural arterial electrical stimulation were obtained. A 1 h continuous infusion of bumetanide (0.1 micrograms ml-1) increased the sensitivity of rat kidney vessels to noradrenaline, an effect also seen when bumetanide and flurbiprofen (6 micrograms ml-1) were simultaneously perfused. In the rabbit there was a decreased sensitivity to both electrical stimulation and noradrenaline. A 1 h continuous infusion of frusemide (6 micrograms ml-1) only altered the effects of electrical stimulation. An increased sensitivity in the rat (abolished by flurbiprofen) and a decreased sensitivity in the rabbit kidney was observed. A 1 h continuous infusion of prostaglandin (PG)E2 (2 ng ml-1) increased the sensitivity of rat kidney to both types of stimuli but caused a reduction in the responsiveness of the rabbit kidney to electrical stimuli only. Addition of flurbiprofen only slightly modified these results. The results emphasize and confirm the fundamental difference in reactivity of the rat and rabbit kidney. Bumetanide and frusemide, two ostensibly similar loop diuretics, show significantly different effects on these preparations suggesting that any modification by non-steroidal anti-inflammatory drugs cannot wholly be explained by similar PGE2 induced haemodynamic changes.