Atrial natriuretic peptide and renal cGMP in rats with experimental heart failure.
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)
Abassi
Z
Z
Rappaport Institute for Research in the Medical Sciences, Faculty of Medicine, Technion, Haifa, Israel.
Burnett
J C
JC
Grushka
E
E
Hoffman
A
A
Haramati
A
A
Winaver
J
J
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
D009320:Atrial Natriuretic Factor; D006152:Cyclic GMP