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Effect of the ANF analog A68828 in cisplatin-induced acute renal failure.

Abstract
Experiments were conducted to determine the effects of the reduced-size atrial natriuretic factor (ANF) analog, A68828, on renal function in rats with cisplatin (CP)-induced acute renal failure. CP was given as a single intraperitoneal injection (7.5 mg/kg) 3 days before experiments. In separate groups of rats, the renal response to intravenous infusion of A68828 at 3, 10 or 30 micrograms/kg/min or ANF[1-28] at 0.03, 0.1 or 0.3 micrograms/kg/min for 2 hr was evaluated. Another group of CP-treated rats were infused with the vehicle (0.1% bovine serum albumin in 0.9% NaCl). CP treatment resulted in a marked decline in glomerular filtration rate (GFR), arterial pressure, heart rate and reabsorption of water and electrolytes compared to untreated control animals. Infusion of A68828 produced a dose-dependent improvement in the glomerular filtration rate. The highest dose of A68828 produced a nearly 3-fold increase in the glomerular filtration rate, whereas arterial pressure was decreased; heart rate was unchanged. Despite producing a significant diuresis and natriuresis, net tubular reabsorption of water and sodium was also increased. Similar dose-dependent effects were observed with the native peptide, ANF[1-28]. These data indicate that infusion of the reduced-sized analog of ANF, A68828, can significantly improve glomerular and tubular function in rats with acute renal failure induced by CP.
AuthorsD M Pollock, M Holst, T J Opgenorth
JournalThe Journal of pharmacology and experimental therapeutics (J Pharmacol Exp Ther) Vol. 257 Issue 3 Pg. 1179-83 (Jun 1991) ISSN: 0022-3565 [Print] United States
PMID1828504 (Publication Type: Comparative Study, Journal Article)
Chemical References
  • A 68828
  • Atrial Natriuretic Factor
  • Cisplatin
  • Potassium
Topics
  • Acute Kidney Injury (chemically induced, drug therapy)
  • Amino Acid Sequence
  • Animals
  • Atrial Natriuretic Factor (pharmacology)
  • Cisplatin (antagonists & inhibitors)
  • Dose-Response Relationship, Drug
  • Glomerular Filtration Rate (drug effects)
  • Hemodynamics (drug effects)
  • Kidney (drug effects, physiopathology)
  • Male
  • Molecular Sequence Data
  • Natriuresis (drug effects)
  • Potassium (urine)
  • Rats
  • Rats, Inbred Strains
  • Renal Circulation (drug effects)

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