title: Tubular resistance to furosemide contributes to the attenuated diuretic response in nephrotic rats.
abstract: A blunted response to loop diuretics frequently occurs in nephrotic syndrome (NS). Observations that nephrotic humans have reduced sodium excretion at normal rates of diuretic excretion have suggested that tubular resistance to the drug may contribute to diuretic resistance. To determine if tubular resistance to furosemide exists in NS, late proximal and early distal tubular micropuncture was performed in rats with puromycin aminonucleoside-induced NS and in control rats after an i.v. bolus dose of furosemide of 1 mg/kg body wt. Absolute and fractional urinary sodium excretions were less (P less than 0.05) in NS rats than in control rats after furosemide. Inulin clearance and total urinary furosemide excretion, however, were not different between groups. Thus, similar to reports in humans, the urinary sodium-to-furosemide excretion ratio was less (P less than 0.05) in NS than in control rats. Single-nephron GFR and chloride delivery to late proximal sites were not different between groups after furosemide. In contrast, absolute and fractional chloride deliveries to early distal sites were less (P less than 0.05) in NS rats after furosemide. Calculated loop chloride reabsorption after furosemide was greater (P less than 0.05) in NS than in control rats when expressed either as percentage of filtered load (39.4 +/- 3.1 versus 28.2 +/- 2.0%) or delivered load (67.9 +/- 4.7 versus 48.3 +/- 3.0%). Loop fluid reabsorption was not different between groups. Thus, loop chloride reabsorption is inhibited to a lesser extent by i.v. furosemide in NS than in normal rats.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Medicine, University of Mississippi Medical Center, Jackson 39216-4505.
authors.forename: K A
authors.initials: KA
authors.lastname: Kirchner
authors.forename: J R
authors.initials: JR
authors.lastname: Voelker
authors.forename: D C
authors.initials: DC
authors.lastname: Brater
mesh_terms: D000818:Animals; D002712:Chlorides / Q000652:urine; D004231:Diuresis / Q000187:drug effects*; D004351:Drug Resistance; D005665:Furosemide / Q000494:pharmacology* / Q000627:therapeutic use; D007684:Kidney Tubules / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009404:Nephrotic Syndrome / Q000139:chemically induced / Q000150:complications / Q000188:drug therapy / Q000378:metabolism*; D011507:Proteinuria / Q000209:etiology; D011692:Puromycin Aminonucleoside / Q000633:toxicity; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000652:urine
chemical_list: D002712:Chlorides; D011692:Puromycin Aminonucleoside; D005665:Furosemide; D012964:Sodium