Effect of acetylcholine on the early phase of reversible norepinephrine-induced acute renal failure

Effect of acetylcholine on the early phase of reversible norepinephrine-induced acute renal failure. A reversible model of norepinephrine-induced (NE) acute renal failure (ARF) was developed in Sprague-Dawley rats. At 48 hr after norepinephrine infusion into the renal artery, renal blood flow (RBF) had returned spontaneously to control values, but inulin clearance (C In ) was only 9% of control. Mean proximal tubular pressure (P T ) was 22 ±6 mm Hg (control, 9 ± 1 mm Hg, P > 0.001). Recovery of 14 C-inulin microperfused from early proximal to mid or late distal tubule was 96 ± 5%. Using this model of acute renal failure, we infused acetylcholine (ACh) into the renal artery 1 hr after the cessation of NE infusion to determine the effects on renal function if RBF could be restored to normal shortly after the ischemic insult. ACh was infused for 4 to 6 hr. Anuria persisted despite return of RBF (control value of 6.52 ± 0.95 vs. postacetylcholine value of 6.21 ± 1.02 ml/min). Tubules were dilated with minimal spontaneous movement of injected oil. P T was 41 ± 14 mm Hg (control, 10 ± 1 mm Hg, P GC ) was 68 ± 15 mm Hg (control, 49 ± 4 mm Hg, P EA ) was 45 ± 12 mm Hg (control, 14 ± 3 mm Hg, P AA ) and efferent arteriolar protein content (C EA ) was 0.04 ± 0.03. Nephron filtration could be increased to a normal range by normalizing the glomerular capillary to proximal tubular hydraulic pressure (ΔP) with a decompression pipette in the proximal tubule. The increase in filtration rate was directly related to the decrement in intratubular pressure (r = 0.998, P 14 C-inulin was detected by microperfusion from the early proximal to mid or late distal convoluted tubule. Homogeneous intraluminal deposits were found diffusely scattered throughout nephron segments beyond the proximal tubules including the loops of Henle. Transmission and scanning electron microscopy of samples of glomeruli was normal. We conclude that in the first few hours after the onset of a reversible NE-induced acute renal failure model in the rat, recovery of renal blood flow with acetylcholine infusion does not improve inulin clearance because of intratubular deposits that cause tubular obstruction. Effet de l'acetylcholine au cours de la phase initiale de l'insuffisance renale aigue induite par la norepineephrine. Un modele d'insuffisance renale aigue (ARF) reversible obtenue par la norepineephrine (NE) a ete developpe chez des rats Sprague-Dawley. Quarante-huit heures apres la perfusion de NE dans l'artere renale le debit sanguin renal (RBF) est revenu spontanement aux valeurs controles alors que la clearance de l'inuline (C in ) n'est qu'a 9% des controles. La pression tubulaire proximale moyenne (P T ) est de 22 + 6 mm Hg (controles, 9 ± 1 mm Hg, P 14 C microperfusee du proximal precoce au distal moyen ou tardif est de 96 ± 5%. Avec ce modele d'insuffisance renale aigue, l'acetylcholine (ACh) a ete perfusee dans l'artere renale une heure apres l'arret de la perfusion de NE pour etudier les consequences sur la fonction renale du retour a la normale de RBF rapidement apres l'ischemie. ACh a ete' perfuse pendant 4 â 6 heures. L'anurie a persiste malgre la normalisation de RBF (controles, 6,52 ± 0,95; post-ACh : 6,21 ± 1,02 ml/min). Les tubules etaient dilates et les mouvements spontanes de l'huile injectee etaient minimes. P T etait de 41 ± 14 mm Hg (controles : 10 ± 1 mm Hg, P EA ) etait de 45 ± 12 mm Hg (controles, 14 ± 3 mm Hg, P AA ) et arteriolaire efferente (C EA ) etait de 0,04 ± 0,03. La filtration par nephron a pu etre augmentee a une valeur normale en normalisant la difference de pression dans le capillaire glomerulaire par rapport a la pression hydraulique tubulaire proximale (ΔP) au moyen d'une pipette de decompression dans le tube proximal. L'augmentation du debit de filtration etait alors proportionnelle a la diminution de la pression intra-tubulaire (r = 0,998, P 14 C inuline au cours des microperfusions du proximal precoce au tube contourne distal moyen ou tardif. Des depots intraluminaux homogenes ont ete observes repartis de facon diffuse le long des segments du nephron en aval du tube proximal incluant les anses de Henle. La microscopie electronique par transmission et par balayage des glomerules n'a pas montre d'anomalies. Il est conclu que dans les premieres heures apres l'installation d'une ARF reversible induite par NE chez le rat la recuperation d'un RBF normal par la perfusion d'acetylcholine n'ameliore pas la clearance de l'inuline en raison de depots intratubulaires qui determinent une obstruction tubulaire.