Hemodynamic Effects of Furosemide in Isolated Perfused Rat Kidneys

Abstract

In anesthetized dogs, the diuretic furosemide has been shown to increase renal blood flow, an effect which can be blocked by the prostaglandin synthetase inhibitor, indomethacin (1, 2). Furosemide also caused an increase in PGE2 release into renal venous blood and this increase was inhibited by indomethacin (2). These data suggest a relationship between the hemodynamic effect of furosemide and the renal prostaglandins.PGE2 is a vasodilator in the dog kidney; however, Malik and MgGiff (3) demonstrated that this prostaglandin increases renal vascular resistance in the rat. This apparent species difference between the rat and other mammals (4) offers a potential tool for elucidating the relationship between furosemide and PGE2 on renal hemodynamics. If the action of furosemide to dilate the renal vasculature in dogs is dependent on release of PGE2, and if PGE2 is a vasoconstrictor in rats, then furosemide would be expected to decrease renal blood flow in the rat. Alternatively, if the primary effect of furosemide is to produce hemodynamic changes which secondarily influence prostaglandin synthesis, furosemide might increase renal blood flow in rats as it does in dogs.The purpose of this investigation was to determine the effect of furosemide on renal vascular resistance and to elucidate the interactions between this diuretic and PGE2 in isolated perfused rat kidneys. Since the reninangiotensin system may also influence the renal vasculature, experiments were performed to evaluate interactions between this system and PGE2 and furosemide.Methods. All experiments were performed on kidneys obtained from male, Sprague-Dawley rats (Spartan Research Animals, Inc., Haslett, MI) weighing 300-375 g. Rats were ' Supported in part by USPHS Grant Nos. AM 10913 Medical Student Research Fellow of the Michigan and HD 06290. Heart Association.anesthetized with 50 mg/kg sodium pentobarbital, intraperitoneally. The abdomen was opened by a midline incision and the right kidney, the right renal artery, and the abdominal aorta were exposed. All rats received 3 mg of heparin via the femoral vein five minutes prior to cannulation of the inferior vena cava. The right ureter and the inferior vena cava were cannulated for collection of urine and venous effluent, respectively. Following cannulation of the right renal artery, perfusion with modified Tyrode's solution containing 1% inulin and saturated with a 95% 02-5% C02 mixture was immediately initiated using a Harvard Apparatus Peristaltic Pump, Model 1203. Tyrode's solution was modified as follows: 124 mM NaC1, 2.7 mM KC1, 1.8 mM CaC12, 1.1 mM MgC12, 25 mM NaHC03, 0.42 mM NaHP04, and 5.6 mM D-glucose. The kidney was excised from the animal, placed on a nylon covered ring and covered with cotton gauze moistened with modified Tyrode's solution. Temperature of the perfusate and kidney was maintained at 35-39' with a heat lamp. The perfusate did not recirculate.An equilibrium period followed attachment of the isolated kidney to the perfusion apparatus. During this time the flow rate was adjuste...

Age-dependent cardiovascular, renal and endocrine responses to furosemide in conscious lambs

“…Previous experiments in adult animals and humans have provided evidence that this renal haemodynamic response to furosemide results from an increase in prostaglandins of the E series 22 . For example, the RBF response to furosemide is attenuated by pretreatment with indomethacin 23,24 . Age‐dependent effects of furosemide on RBF could result from differential effects of furosemide on prostaglandin biosynthesis.…”

“…22 For example, the RBF response to furosemide is attenuated by pretreatment with indomethacin. 23,24 Age-dependent effects of furosemide on RBF could result from differential effects of furosemide on prostaglandin biosynthesis. Because furosemide also enhances the release of endothelial kinins and nitric oxide, at least in cultured bovine aortic endothelial cells, 25 age-dependent effects of furosemide on RBF could also result from differences in the release of vasodilatory agents other than prostaglandins.…”

Intrarenal dopamine participation in frusemide diuretic and natriuretic responses to frusemide

“…GFR was not affected by frusemide in the same way in all preparations. It has been proposed that frusemide stimulates renin release in isolated perfused kidneys under a constant pressure perfusion (Moore & Hook, 1978). Different renin levels could be expected in the preparations.…”