Effect of furosemide on renal autoregulation. The effect of furosemide administration on renal blood flow (RBF) and glomerular filtration rate (GFR) autoregulation was examined in pentobar-bital-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 mm 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 mI/ming) and averaged 5.20 0.6 and 6.10 0.7 mllmmng, respectively. After 60 mm 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 mm. 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 (2mg/kg). Forty-five minutes following adminstration of either PG synthesis inhibitor, RBF autoregulation was still demonstrable; overall RBF, however, decreased (P< 0.01) from 3.9 0.2 to 2.6 0.2 mllming at any RPP between 140 and 100 mm Hg. Fifteen minutes after furosemide infusion, RBF autoregulatory capability was again abolished, and RBF rose from 2.6 0.2 to 4.0 0.5 and to 3.6 0.4 mI/ming (each, P< 0.01) at RPP of 140 and 120 mm Hg, respectively. 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 mm. PG's do not appear to be directly involved in normal autoregulatory response nor in inducing renal vasodilatation following furosem-ide. 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 furosémide stir l'autoregulation rénale. L'effet du furosémide sur l'autorégulation du debit sanguin renal (RBF) et du debit de filtration glomérulaire (GFR) a été étudié, chez des chiens anesthésiés par le pentobarbital, au cours d'une constriction unilatérale de l'artère rénale qui a réduit la pression de perfusion rénale (RPP) de 140 a 40 mm Hg par décréments de 20 mm Hg. Dans le premier group d'animaux, a une RPP supérieure a 80 mm Hg, l'autoregulation de RBF ne s' exerce plus 15 mm après le debut de Ia perfusion de furosémide (dose initiale, 5 mg/kg; et dose d'entretien, 5 mg'kg/hr), puisque les modifications de RPP sont