Effect of furosemide on renal autoregulation

Effect of furosemide on renal autoregulation. The effect of furosemide administration on renal blood flow (RBF) and glomerular fitration rate (GFR) autoregulation was examined in pentobarbital-anesthetized dogs during unilateral renal artery constriction, which reduced renal perfusion pressure (RPP) in 20 mm Hg decrements from 140 to 40 mm Hg. In the first group of animals, at RPP above 80 mm Hg, RBF autoregulation was absent 15 min after initiating furosemide infusion (5 mg/kg of body wt, prime; and 5 mg/kg/hr), as changes in RPP were accompanied by proportional changes in RBF. At both 120 and 140 mm Hg, RBF was significantly greater than control (3.96 ± 0.4 ml/min·g) and averaged 5.20 ± 0.6 and 6.10 ± 0.7 ml/min·g, respectively. After 60 min of continuous furosemide infusion, however, autoregulatory ability as well as RBF returned to control values. GFR, estimated from inulin extraction and renal blood plasma flow, autoregulated during control and at both 15 and 60 min. To test the hypothesis that prostaglandins (PG) may mediate the early vasodilatation observed during furosemide infusion, a second series of experiments were performed in which animals were pretreated with either indomethacin (10 mg/kg) or RO 20-5720 (2 mg/kg). Forty-five minutes following adminstration of either PG synthesis inhibitor, RBF autoregulation was still demonstrable; overall RBF, however, decreased (P Summary . This study has demonstrated that the excellent RBF autoregulatory capability of dogs can be abolished early after furosemide administration; this acute diuretic-related abolishment of vascular responsiveness is reversed within 60 min. PG's do not appear to be directly involved in normal autoregulatory response nor in inducing renal vasodilatation following furosemide. Finally, GFR autoregulation is well maintained during furosemide administration. The mechanism for the early loss of renal autoregulatory ability remains obscure. Changes in ECF volume, renin secretory rate, or plasma furosemide concentrations do not appear to be directly responsible. Effet du furosemide sur l'autoregulation renale. L'effet du furosemide sur l'autoregulation du debit sanguin renal (RBF) et du debit de filtration glomerulaire (GFR) a ete etudie, chez des chiens anesthesies par le pentobarbital, au cours d'une constriction unilateral de l'artere renale qui a reduit la pression de perfusion renale (RPP) de 140 a 40 mm Hg par decrements de 20 mm Hg. Dans le premier group d'animaux, a une RPP superieure a 80 mm Hg, l'autoregulation de RBF ne s'exerce plus 15 min apres le debut de la perfusion de furosemide (dose initiale, 5 mg/kg; et dose d'entretien, 5 mg/kg/hr), puisque les modifications de RPP sont accompagnees par des modifications proportionnelles de RBF. A 120 et 140 mm Hg de RPP, RBF est significativement superieur aux valeurs controles (3,96 ± 0,4 ml/min·g) les valeurs moyennes sont 5,20 ± 0,6 et 6,10 ± 0,7 ml/min·g respectivement. Soixante minutes apres le debut de la perfusion de furosemide, cependant, la capacite d'autoregulation et RBF reviennent aux valeurs controles. Le GFR, calcule a partir de l'extraction de la creatinine et du debit plasmatique renal, est autoregule au cours de la periode controle et aussi bien a 15 qu'a 60 min. Pour etudier l'hypothese selon laquelle les prostaglandines (PG) peuvent etre le mediateur de la vasodilatation precoce observee au cours de l'administration de furosemide, une seconde serie d'experiences a ete realisee au cours de laquelle les animaux ont prealablement ete traites soit par l'indomethacine (10 mg/kg) ou RO 20-5720 (2 mg/kg). Quarante cinq minutes apres l'administration de l'un ou l'autre inhibiteur de la synthese de PG l'autoregulation est encore observee mais le RBF global est diminue (P