title: Atrial natriuretic peptide and renal cGMP in rats with experimental heart failure.
abstract: Rats with chronic aortocaval (AV) fistula, an experimental model of congestive heart failure, display high plasma levels of atrial natriuretic factor (ANF) and a blunted natriuretic response to ANF infusion. We previously reported that rats with AV fistula either develop progressive sodium retention (urinary sodium excretion, UNaV less than 100 microeq/24 h) or compensate (UNaV greater than 1,200 microeq/24 h). To gain further insight into the mechanism of renal hyporesponsiveness to ANF, we evaluated the effect of ANF on renal guanosine 3',5'-cyclic monophosphate (cGMP) production in sham-operated control rats and in the two groups of rats with AV fistula. Infusion of synthetic ANF-(99-126) (at either 10 or 50 micrograms.kg-1.h-1) resulted in a reduced fractional sodium excretion (P less than 0.05) in both compensated rats (0.7 +/- 0.2 and 7.9 +/- 1.6%) and sodium-retaining rats (0.3 +/- 0.1 and 0.5 +/- 0.1%) compared with controls (8.5 +/- 1.2 and 13.7 +/- 2.3% for low and high doses, respectively). Similarly, urinary cGMP excretion corrected by glomerular filtration rate (UcGMPV/GFR) during low-dose ANF infusion was significantly reduced (P less than 0.05) in both groups with AV fistula (compensated: 39 +/- 10 pmol/ml; sodium-retaining: 55 +/- 13 pmol/ml) compared with controls (115 +/- 16 pmol/ml). During high-dose ANF infusion, compensated rats, but not sodium-retaining rats, displayed a significant increase in UcGMPV/GFR. The differences in UcGMPV/GFR are probably not due to variations in urine flow because furosemide infusion to a separate group of rats with AV fistula increased urine flow approximately eightfold but did not increase UcGMPV/GFR.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Rappaport Institute for Research in the Medical Sciences, Faculty of Medicine, Technion, Haifa, Israel.
authors.forename: Z
authors.initials: Z
authors.lastname: Abassi
authors.forename: J C
authors.initials: JC
authors.lastname: Burnett
authors.forename: E
authors.initials: E
authors.lastname: Grushka
authors.forename: A
authors.initials: A
authors.lastname: Hoffman
authors.forename: A
authors.initials: A
authors.lastname: Haramati
authors.forename: J
authors.initials: J
authors.lastname: Winaver
mesh_terms: D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D006152:Cyclic GMP / Q000378:metabolism* / Q000652:urine; D004231:Diuresis; D004305:Dose-Response Relationship, Drug; D006333:Heart Failure / Q000378:metabolism* / Q000652:urine; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D009320:Atrial Natriuretic Factor; D006152:Cyclic GMP