title: Equimolar doses of atrial and brain natriuretic peptides and urodilatin have differential renal actions in overt experimental heart failure.
abstract: A hallmark of overt congestive heart failure (CHF) is attenuated cGMP production by endogenous atrial natriuretic peptide (ANP) with renal resistance to ANP. ANP and brain natriuretic peptides (BNP) are of myocardial origin, whereas urodilatin (Uro) is thought to be derived from kidney. All three peptides are agonists to the natriuretic peptide-A receptor. Our objective was to compare the cardiorenal and humoral actions of ANP, BNP, and Uro in experimental overt CHF. We determined cardiorenal and humoral actions of 90 min of intravenous equimolar infusion of ANP, BNP, and Uro (2 and 10 pmol.kg-1.min-1) in three separate groups of anesthetized dogs with rapid ventricular pacing-induced overt CHF (240 beats/min for 10 days). BNP resulted in increases in urinary sodium excretion (U(Na)V) (2.2+/-0.7 to 164+/-76 microeq/min, P<0.05) and glomerular filtration rate (GFR) (27+/-4 to 52+/-11 ml/min, P<0.05) that were greater than those with Uro (P<0.05), whereas ANP did not result in increases in U(Na)V or GFR. Increases in plasma cGMP (25+/-2 to 38+/-2 pmol/ml, P<0.05) and urinary cGMP excretion with BNP (1,618+/-151 to 6,124+/-995 pmol/min, P<0.05) were similar to those with Uro; however, there was no change with ANP. Cardiac filling pressures were reduced in all three groups. These studies also support the conclusion that in experimental overt CHF, renal resistance to natriuretic peptides in increasing rank order is BNP<Uro<ANP.
authors.affiliation: Cardiorenal Research Laboratory, Guggenheim 915, Mayo Clinic and Foundation, 200 First St SW, Rochester, MN 55905, USA. chen.horng@mayo.edu
authors.forename: Horng H
authors.initials: HH
authors.lastname: Chen
authors.forename: Alessandro
authors.initials: A
authors.lastname: Cataliotti
authors.forename: John A
authors.initials: JA
authors.lastname: Schirger
authors.forename: Fernando L
authors.initials: FL
authors.lastname: Martin
authors.forename: John C
authors.initials: JC
authors.lastname: Burnett
mesh_terms: D000818:Animals; D009320:Atrial Natriuretic Factor / Q000097:blood / Q000494:pharmacology / Q000502:physiology* / Q000652:urine; D006152:Cyclic GMP / Q000097:blood / Q000652:urine; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D006333:Heart Failure / Q000503:physiopathology*; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D007668:Kidney / Q000187:drug effects / Q000502:physiology; D008297:Male; D020097:Natriuretic Peptide, Brain / Q000097:blood / Q000494:pharmacology / Q000502:physiology* / Q000652:urine; D010446:Peptide Fragments / Q000097:blood / Q000494:pharmacology / Q000502:physiology* / Q000652:urine
chemical_list: D010446:Peptide Fragments; D020097:Natriuretic Peptide, Brain; C056452:Ularitide; D009320:Atrial Natriuretic Factor; D006152:Cyclic GMP