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Intrarenal effects of ecadotril during acute volume expansion in dogs with congestive heart failure.
J Pharmacol Exp Ther. 2000 Jun; 293(3):989-95.JP

Abstract

Neutral endopeptidase 24.11 (NEP) inhibitors are known to have vascular, diuretic, and natriuretic effects that may be helpful in the treatment of congestive heart failure (CHF). Most NEP inhibitors may act principally through intrarenal mechanisms, which are not completely understood. The purpose of this study was to determine the principal renal effects of the NEP inhibitor ecadotril in dogs with progressive CHF induced by rapid ventricular pacing. Renal function was measured before, during, and after acute i.v. infusion of normal saline in a total of six dogs during normal cardiac function, early left ventricular dysfunction, and overt CHF. During overt CHF, each dog was treated with either ecadotril or placebo orally for 1 week. Parameters measured included glomerular filtration rate, renal blood flow, urine output, sodium clearance, sodium fractional excretion, and proximal and distal sodium reabsorption. Ecadotril treatment resulted in increased urine output, sodium clearance, and renal sodium excretion relative to placebo-treated controls. The principal intrarenal effect of ecadotril was decreased distal renal tubular sodium reabsorption. Both glomerular filtration rate and renal blood flow declined during overt CHF and were unaffected by ecadotril treatment. The results of this study are consistent with the principal action of ecadotril occurring by way of intrarenal events as opposed to changes in renal hemodynamics. The principal effect of ecadotril on distal tubular sodium reabsorption suggests that inhibition of NEP activity in the proximal renal tubules may allow increased binding of filtered atrial natriuretic peptide to natriuretic peptide receptor sites in the distal renal tubules and collecting ducts.

Authors+Show Affiliations

University of Illinois, College of Veterinary Medicine, Urbana-Champaign 61802, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

10869402

Citation

Solter, P, et al. "Intrarenal Effects of Ecadotril During Acute Volume Expansion in Dogs With Congestive Heart Failure." The Journal of Pharmacology and Experimental Therapeutics, vol. 293, no. 3, 2000, pp. 989-95.
Solter P, Sisson D, Thomas W, et al. Intrarenal effects of ecadotril during acute volume expansion in dogs with congestive heart failure. J Pharmacol Exp Ther. 2000;293(3):989-95.
Solter, P., Sisson, D., Thomas, W., & Goetze, L. (2000). Intrarenal effects of ecadotril during acute volume expansion in dogs with congestive heart failure. The Journal of Pharmacology and Experimental Therapeutics, 293(3), 989-95.
Solter P, et al. Intrarenal Effects of Ecadotril During Acute Volume Expansion in Dogs With Congestive Heart Failure. J Pharmacol Exp Ther. 2000;293(3):989-95. PubMed PMID: 10869402.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Intrarenal effects of ecadotril during acute volume expansion in dogs with congestive heart failure. AU - Solter,P, AU - Sisson,D, AU - Thomas,W, AU - Goetze,L, PY - 2000/6/28/pubmed PY - 2000/7/25/medline PY - 2000/6/28/entrez SP - 989 EP - 95 JF - The Journal of pharmacology and experimental therapeutics JO - J. Pharmacol. Exp. Ther. VL - 293 IS - 3 N2 - Neutral endopeptidase 24.11 (NEP) inhibitors are known to have vascular, diuretic, and natriuretic effects that may be helpful in the treatment of congestive heart failure (CHF). Most NEP inhibitors may act principally through intrarenal mechanisms, which are not completely understood. The purpose of this study was to determine the principal renal effects of the NEP inhibitor ecadotril in dogs with progressive CHF induced by rapid ventricular pacing. Renal function was measured before, during, and after acute i.v. infusion of normal saline in a total of six dogs during normal cardiac function, early left ventricular dysfunction, and overt CHF. During overt CHF, each dog was treated with either ecadotril or placebo orally for 1 week. Parameters measured included glomerular filtration rate, renal blood flow, urine output, sodium clearance, sodium fractional excretion, and proximal and distal sodium reabsorption. Ecadotril treatment resulted in increased urine output, sodium clearance, and renal sodium excretion relative to placebo-treated controls. The principal intrarenal effect of ecadotril was decreased distal renal tubular sodium reabsorption. Both glomerular filtration rate and renal blood flow declined during overt CHF and were unaffected by ecadotril treatment. The results of this study are consistent with the principal action of ecadotril occurring by way of intrarenal events as opposed to changes in renal hemodynamics. The principal effect of ecadotril on distal tubular sodium reabsorption suggests that inhibition of NEP activity in the proximal renal tubules may allow increased binding of filtered atrial natriuretic peptide to natriuretic peptide receptor sites in the distal renal tubules and collecting ducts. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/10869402/Intrarenal_effects_of_ecadotril_during_acute_volume_expansion_in_dogs_with_congestive_heart_failure_ L2 - http://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=10869402 DB - PRIME DP - Unbound Medicine ER -