Atrial natriuretic peptide and renal cGMP in rats with experimental heart failure

Z. Abassi, John C Jr. Burnett, E. Grushka, A. Hoffman, A. Haramati, J. Winaver

Research output: Contribution to journalArticle

31 Citations (Scopus)

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, U(Na)V < 100 μeq/24 h) or compensate (U(Na)V > 1,200 μeq/ 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 μg·kg-1·h-1) resulted in a reduced fractional sodium excretion (P < 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 (U(cGMP)V/GFR) during low-dose ANF infusion was significantly reduced (P < 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 U(cGMP)V/GFR. The differences in U(cGMP)V/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 U(cGMP)V/GFR. In contrast to the effects in vivo, incubation of glomeruli in vitro with increasing concentration of ANF (10-11 to 10-6 M in the presence of 1 mM 3-isobutyl-l-methylxanthine) resulted in similar increases in cGMP content in glomeruli derived from all three groups of rats (controls: 2.4 ± 0.3 to 9.1 ± 1.0 pmol/mg protein; compensated: 2.5 ± 0.2 to 8.6 ± 0.7 pmol/mg protein; sodium-retaining: 3.0 ± 0.2 to 7.4 ± 0.7 pmol/mg protein). Thus, despite an intact capacity of glomeruli to generate cGMP in response to ANF, the ANF-induced increase in U(cGMP)V in vivo is attenuated in experimental heart failure. These findings suggest that the hyporesponsiveness to ANF in heart failure may involve factors present in vivo that impede the action of ANF on its second messenger system.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume261
Issue number4 30-4
StatePublished - 1991
Externally publishedYes

Fingerprint

Atrial Natriuretic Factor
Heart Failure
Kidney
Sodium
Fistula
Urine
Proteins
Urinary Retention
Cyclic GMP
Furosemide
Second Messenger Systems
Glomerular Filtration Rate
Theoretical Models

Keywords

  • aortacaval fistula
  • atrial natriuretic factor
  • kidney function

ASJC Scopus subject areas

  • Physiology

Cite this

Atrial natriuretic peptide and renal cGMP in rats with experimental heart failure. / Abassi, Z.; Burnett, John C Jr.; Grushka, E.; Hoffman, A.; Haramati, A.; Winaver, J.

In: American Journal of Physiology - Regulatory Integrative and Comparative Physiology, Vol. 261, No. 4 30-4, 1991.

Research output: Contribution to journalArticle

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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, U(Na)V < 100 μeq/24 h) or compensate (U(Na)V > 1,200 μeq/ 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 μg·kg-1·h-1) resulted in a reduced fractional sodium excretion (P < 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 (U(cGMP)V/GFR) during low-dose ANF infusion was significantly reduced (P < 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 U(cGMP)V/GFR. The differences in U(cGMP)V/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 U(cGMP)V/GFR. In contrast to the effects in vivo, incubation of glomeruli in vitro with increasing concentration of ANF (10-11 to 10-6 M in the presence of 1 mM 3-isobutyl-l-methylxanthine) resulted in similar increases in cGMP content in glomeruli derived from all three groups of rats (controls: 2.4 ± 0.3 to 9.1 ± 1.0 pmol/mg protein; compensated: 2.5 ± 0.2 to 8.6 ± 0.7 pmol/mg protein; sodium-retaining: 3.0 ± 0.2 to 7.4 ± 0.7 pmol/mg protein). Thus, despite an intact capacity of glomeruli to generate cGMP in response to ANF, the ANF-induced increase in U(cGMP)V in vivo is attenuated in experimental heart failure. These findings suggest that the hyporesponsiveness to ANF in heart failure may involve factors present in vivo that impede the action of ANF on its second messenger system.",
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N2 - 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, U(Na)V < 100 μeq/24 h) or compensate (U(Na)V > 1,200 μeq/ 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 μg·kg-1·h-1) resulted in a reduced fractional sodium excretion (P < 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 (U(cGMP)V/GFR) during low-dose ANF infusion was significantly reduced (P < 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 U(cGMP)V/GFR. The differences in U(cGMP)V/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 U(cGMP)V/GFR. In contrast to the effects in vivo, incubation of glomeruli in vitro with increasing concentration of ANF (10-11 to 10-6 M in the presence of 1 mM 3-isobutyl-l-methylxanthine) resulted in similar increases in cGMP content in glomeruli derived from all three groups of rats (controls: 2.4 ± 0.3 to 9.1 ± 1.0 pmol/mg protein; compensated: 2.5 ± 0.2 to 8.6 ± 0.7 pmol/mg protein; sodium-retaining: 3.0 ± 0.2 to 7.4 ± 0.7 pmol/mg protein). Thus, despite an intact capacity of glomeruli to generate cGMP in response to ANF, the ANF-induced increase in U(cGMP)V in vivo is attenuated in experimental heart failure. These findings suggest that the hyporesponsiveness to ANF in heart failure may involve factors present in vivo that impede the action of ANF on its second messenger system.

AB - 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, U(Na)V < 100 μeq/24 h) or compensate (U(Na)V > 1,200 μeq/ 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 μg·kg-1·h-1) resulted in a reduced fractional sodium excretion (P < 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 (U(cGMP)V/GFR) during low-dose ANF infusion was significantly reduced (P < 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 U(cGMP)V/GFR. The differences in U(cGMP)V/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 U(cGMP)V/GFR. In contrast to the effects in vivo, incubation of glomeruli in vitro with increasing concentration of ANF (10-11 to 10-6 M in the presence of 1 mM 3-isobutyl-l-methylxanthine) resulted in similar increases in cGMP content in glomeruli derived from all three groups of rats (controls: 2.4 ± 0.3 to 9.1 ± 1.0 pmol/mg protein; compensated: 2.5 ± 0.2 to 8.6 ± 0.7 pmol/mg protein; sodium-retaining: 3.0 ± 0.2 to 7.4 ± 0.7 pmol/mg protein). Thus, despite an intact capacity of glomeruli to generate cGMP in response to ANF, the ANF-induced increase in U(cGMP)V in vivo is attenuated in experimental heart failure. These findings suggest that the hyporesponsiveness to ANF in heart failure may involve factors present in vivo that impede the action of ANF on its second messenger system.

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