title: Clearance of human brain natriuretic peptide in rabbits; effect of the kidney, the natriuretic peptide clearance receptor, and peptidase activity.
abstract: Although the synthetic version of the cardiac peptide human brain natriuretic peptide (hBNP) has demonstrated beneficial cardiovascular effects in clinical studies, little is known about mechanisms governing its elimination from the blood. This study measured the role of the kidney, the natriuretic peptide clearance (NP-C) receptor, and peptidase digestion on the elimination of synthetic hBNP from the plasma compartment of rabbits. The estimated plasma steady state resulting from a continuous i.v. infusion was achieved within 50 min and was related in a linear manner with the infusion rate of the drug. Complete restriction of kidney blood flow by bilateral suture-ligation of the renal arteries compared with sham-treated animals reduced the clearance of hBNP by approximately half (24 +/- 9 ml/min versus 47 +/- 14 ml/min, respectively, p <. 007). Pharmacological blockade of the NP-C receptor with a clearance receptor-specific analog of atrial natriuretic peptide increased in a statistically significant and dose-related manner the plasma steady-state level of hBNP during continuous i.v. infusion of hBNP (maximum effect of 1.9 +/- 0.3-fold, p <.01). The peptidase inhibitor phosphoramidon increased in a dose-related manner the plasma steady-state level of hBNP 1.7 +/- 0.4-fold during continuous i.v. infusion of hBNP in rabbits. These data suggest that the kidney, the NP-C receptor, and peptidases are all important in the elimination of hBNP from the plasma compartment.
authors.affiliation: Scios Incorporated, Mountain View, California, USA.
authors.forename: R
authors.initials: R
authors.lastname: Almirez
authors.forename: A A
authors.initials: AA
authors.lastname: Protter
mesh_terms: D000818:Animals; D006020:Glycopeptides / Q000494:pharmacology; D006801:Humans; D007262:Infusions, Intravenous; D007668:Kidney / Q000378:metabolism*; D008026:Ligation; D008297:Male; D020097:Natriuretic Peptide, Brain / Q000097:blood / Q000493:pharmacokinetics*; D010447:Peptide Hydrolases / Q000378:metabolism*; D011480:Protease Inhibitors / Q000494:pharmacology; D011817:Rabbits; D017461:Receptors, Atrial Natriuretic Factor / Q000378:metabolism*; D012079:Renal Circulation / Q000502:physiology
chemical_list: D006020:Glycopeptides; D011480:Protease Inhibitors; C058930:brain natriuretic peptide receptor; D020097:Natriuretic Peptide, Brain; D010447:Peptide Hydrolases; D017461:Receptors, Atrial Natriuretic Factor; C008890:phosphoramidon