title: Contribution of leg vascular tissues to the overall metabolic clearance of human atrial natriuretic factor (hANF) in man.
abstract: From experimental studies it has been suggested that considerable peripheral clearance of human atrial natriuretic factor (hANF) might occur. In healthy men (n = 7) the peripheral fractional extraction of hANF was about 35% under basal conditions resulting in hANF-uptake across the leg vascular bed of 2.1 +/- 2.4 pMol/min and regional leg clearance rate of 102.6 +/- 88.2 ml/min, which is approximately 2.5% of the total metabolic clearance rate. During a primed constant i.v. infusion of hANF (bolus 100 micrograms; infusion 100 micrograms/h, t = 1h) arterial and venous plasma concentrations of hANF increased about 10-fold (p less than 0.05), however, estimated leg blood flow as well as leg fractional extraction, leg uptake and clearance rates of hANF did not significantly change as compared to baseline. Total metabolic clearance rates and apparent production rates of hANF were 4.05 +/- 1.93 l/min and 84.1 +/- 29.9 pMol/min, respectively. We conclude that in healthy man the leg vascular bed does not play a major regulatory role in the metabolism of exogenously infused hANF. However, our results suggest that the peripheral vasculature is, to a certain extent, involved in the metabolic clearance of endogenous hANF and thus, contributes to the peptide's overall disposal.
authors.affiliation: I. Medizinische Universitätsklinik, Division of Clinical Pharmacology and of Clinical Endocrinology and Diabetes mellitus, Vienna, Austria.
authors.forename: S
authors.initials: S
authors.lastname: Gasic
authors.forename: H
authors.initials: H
authors.lastname: Vierhapper
authors.forename: P
authors.initials: P
authors.lastname: Nowotny
authors.forename: G
authors.initials: G
authors.lastname: Heinz
authors.forename: W
authors.initials: W
authors.lastname: Waldhäusl
mesh_terms: D000328:Adult; D009320:Atrial Natriuretic Factor / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004232:Diuretics / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005263:Femoral Artery / Q000378:metabolism*; D005268:Femoral Vein / Q000378:metabolism*; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008657:Metabolic Clearance Rate; D010446:Peptide Fragments / Q000008:administration & dosage / Q000493:pharmacokinetics*
chemical_list: D004232:Diuretics; D010446:Peptide Fragments; D009320:Atrial Natriuretic Factor