THE ANTIDIURETIC EFFECT OF PNEUMADIN REQUIRES A FUNCTIONAL ARGININE-VASOPRESSIN SYSTEM

Pneumadin is an antidiuretic decapeptide, recently isolated from rat a nd human lung. Bolus intravenous injection of 5 nmol of pneumadin into water-loaded rats caused a rapid and significant antidiuresis and a r eduction in Na+ and Cl- excretion. Pneumadin administration did not al ter mean arterial pressure, right atrial pressure, heart rate or haema tocrit. Bolus intravenous injection of 20 nmol of pneumadin into non-w ater-loaded rats caused a significant increase in arginine vasopressin (AVP) within 10 min. Pneumadin administration also increased circulat ing atrial natriuretic peptide (ANP) but did not alter aldosterone or plasma renin activity levels. Injection of pneumadin into water-loaded Brattleboro rats, which genetically lack circulating AVP, did,not cha nge urine how, confirming that the pneumadin induced antidiuresis is A VP dependent. Radioactive pneumadin was cleared from the circulation w ith a t(1/2)beta of 480.3 s. Radioactive pneumadin, isolated from plas ma, eluted at an altered position on reverse phase HPLC, which indicat ed that the peptide was modified in vivo. This modification was also o bserved when synthetic pneumadin was incubated in rat plasma in vitro. Purification and sequencing of the modified synthetic peptide indicat ed that the modification is not a proteolytic cleavage. These results indicate that pneumadin injected into the rat caused an antidiuresis b y altering circulating AVP levels.