DISPOSITION OF VESSEL DILATOR AND LONG-ACTING NATRIURETIC PEPTIDE IN HEALTHY HUMANS AFTER A ONE-HOUR INFUSION

The present investigation was designed to determine half-lives, distri bution phases and metabolic clearance of two new cardiac peptide hormo nes in humans. Long-acting natriuretic peptide (LANP) and vessel dilat or were infused at 100 ng/kg of b.wt./min concentrations for 60 min wi th their respective concentrations measured by specific radioimmunoass ays in plasma during and for 3 hr after infusion. The half-life of ves sel dilator was 107 min, whereas the half-life of LANP was 28 min. The average time that the respective peptides were retained in the body ( mean residence time) was 214 +/- 34 min for vessel dilator and 178 +/- 12 min for LANP, which indicates that they are widely distributed out side the initial space (i.e., circulation). The metabolic clearance no rmalized to 1.73 m(2) body surface area was 241 ml/min for vessel dila tor and 249 ml/min for LANP. The total body clearance normalized to 1. 73 m(2) body surface area was 130 ml/min for vessel dilator and 293 ml /min for LANP. The significantly (P < .001) longer half-lives and slow er metabolic clearance of LANP and vessel dilator compared with atrial natriuretic factor (half-life, 2.5 min, metabolic clearance, 582-2,58 1 ml/min/1.7 m(2)) explain why these peptides circulate at concentrati ons 15-to 24-fold higher than atrial natriuretic factor in healthy hum ans.