Captopril and ANP: Changes in renal hemodynamics, glomerular-ANP receptors and guanylate cyclase activity in rats with heart failure

R. W. Lee, T. E. Raya, U. Michael, S. Foster, T. Meeks, S. Goldman

Research output: Contribution to journalArticle

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Abstract

To define the renal effects of atrial natriuretic peptide (ANP) in heart failure, we studied rats with heart failure after coronary artery ligation. The rats received either captopril (2 g/l drinking water) or placebo for 4 weeks. Glomerular filtration rate, renal plasma flow, filtration fraction, urine volume, urinary sodium excretion and the percent fractional excretion of sodium were measured before and after an infusion of ANP (0.3 μg/kg/min). To determine whether changes in ANP receptor binding and responsiveness occur in heart failure and after captopril treatment, we performed radioreceptor binding studies and measured guanylate cyclase activity. Atrial natriuretic peptide in sham-operated rats decreased mean arterial pressure from 118 ± 5 to 95 ± 5 mm Hg (P < .001), increased urine volume from 0.06 ± 0.02 to 0.16 ± 0.05 ml/min/kg (P < .05), urinary sodium excretion, 14.2 ± 3.1 to 41.4 ± 8.9 μeq/min/kg (P < .02), filtration fraction from 0.30 ± 0.03 to 0.40 ± 0.4 (P < .05), and the percent fractional excretion of sodium from 0.84 ± 0.19 to 2.85 ± 0.61 (P < .02). Atrial natriuretic peptide in untreated rats with heart failure produced no significant systemic or renal hemodynamic effects. In rats with heart failure treated with captopril, ANP decreased mean arterial pressure from 93 ± 4 to 86 ± 4 mm Hg (P < .05) and increased hematocrit from 50 ± 2 to 52 ± 1 (P < .001). Urinary sodium excretion and percent fractional excretion of sodium also increased from 4.7 ± 0.1 to 9.3 ± 3.7 meq/l (P < .05) and from 0.31 ± 0.09 to 0.84 ± 0.28 (P < .02), meq/l, respectively. Glomerular receptor binding studies showed no significant changes in the dissociation constant and B(max) between sham, untreated heart failure, and captopril-treated heart failure rats. Glomerular membrane guanylate cyclase activity tended to decrease with heart failure and correct with captopril treatment, but these changes were not different. In summary, ANP infusion in heart failure produced a blunted renal hemodynamic response; captopril pretreatment restored the natriuretic effectiveness of ANP infusion. Since glomerular ANP receptor density and membrane guanylate cyclase activity were minimally altered by heart failure or treatment, these data suggest that the primary natriuretic effect of ANP infusion appears to be mediated by extra-glomerular mechanisms.

Original languageEnglish (US)
Pages (from-to)349-354
Number of pages6
JournalJournal of Pharmacology and Experimental Therapeutics
Volume260
Issue number1
StatePublished - Jan 1 1992
Externally publishedYes

Fingerprint

Atrial Natriuretic Factor Receptors
Guanylate Cyclase
Captopril
Atrial Natriuretic Factor
Heart Failure
Hemodynamics
Kidney
Sodium
Arterial Pressure
Urine
Natriuretic Agents
Renal Plasma Flow
Membranes
Glomerular Filtration Rate
Hematocrit
Drinking Water
Ligation
Coronary Vessels
Placebos

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

Cite this

Captopril and ANP : Changes in renal hemodynamics, glomerular-ANP receptors and guanylate cyclase activity in rats with heart failure. / Lee, R. W.; Raya, T. E.; Michael, U.; Foster, S.; Meeks, T.; Goldman, S.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 260, No. 1, 01.01.1992, p. 349-354.

Research output: Contribution to journalArticle

Lee, R. W. ; Raya, T. E. ; Michael, U. ; Foster, S. ; Meeks, T. ; Goldman, S. / Captopril and ANP : Changes in renal hemodynamics, glomerular-ANP receptors and guanylate cyclase activity in rats with heart failure. In: Journal of Pharmacology and Experimental Therapeutics. 1992 ; Vol. 260, No. 1. pp. 349-354.
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N2 - To define the renal effects of atrial natriuretic peptide (ANP) in heart failure, we studied rats with heart failure after coronary artery ligation. The rats received either captopril (2 g/l drinking water) or placebo for 4 weeks. Glomerular filtration rate, renal plasma flow, filtration fraction, urine volume, urinary sodium excretion and the percent fractional excretion of sodium were measured before and after an infusion of ANP (0.3 μg/kg/min). To determine whether changes in ANP receptor binding and responsiveness occur in heart failure and after captopril treatment, we performed radioreceptor binding studies and measured guanylate cyclase activity. Atrial natriuretic peptide in sham-operated rats decreased mean arterial pressure from 118 ± 5 to 95 ± 5 mm Hg (P < .001), increased urine volume from 0.06 ± 0.02 to 0.16 ± 0.05 ml/min/kg (P < .05), urinary sodium excretion, 14.2 ± 3.1 to 41.4 ± 8.9 μeq/min/kg (P < .02), filtration fraction from 0.30 ± 0.03 to 0.40 ± 0.4 (P < .05), and the percent fractional excretion of sodium from 0.84 ± 0.19 to 2.85 ± 0.61 (P < .02). Atrial natriuretic peptide in untreated rats with heart failure produced no significant systemic or renal hemodynamic effects. In rats with heart failure treated with captopril, ANP decreased mean arterial pressure from 93 ± 4 to 86 ± 4 mm Hg (P < .05) and increased hematocrit from 50 ± 2 to 52 ± 1 (P < .001). Urinary sodium excretion and percent fractional excretion of sodium also increased from 4.7 ± 0.1 to 9.3 ± 3.7 meq/l (P < .05) and from 0.31 ± 0.09 to 0.84 ± 0.28 (P < .02), meq/l, respectively. Glomerular receptor binding studies showed no significant changes in the dissociation constant and B(max) between sham, untreated heart failure, and captopril-treated heart failure rats. Glomerular membrane guanylate cyclase activity tended to decrease with heart failure and correct with captopril treatment, but these changes were not different. In summary, ANP infusion in heart failure produced a blunted renal hemodynamic response; captopril pretreatment restored the natriuretic effectiveness of ANP infusion. Since glomerular ANP receptor density and membrane guanylate cyclase activity were minimally altered by heart failure or treatment, these data suggest that the primary natriuretic effect of ANP infusion appears to be mediated by extra-glomerular mechanisms.

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