Stretch-induced atrial natriuretic factor release utilizes a rapidly depleting pool of newly synthesized hormone.
Atrial muscle stretch is widely believed to be the main stimulus for atrial natriuretic factor (ANF) release. However, a few reports have shown that although stretch induces an immediate increase in ANF output, this release rapidly decays even though hormone stores are not significantly depleted. In the present work, this phenomenon was studied in an isolated rat atria preparation using double isotope labeling. The tissue was labeled with [14C]leucine for 3 h followed by a 1-h chase, and then with [3H]leucine for 1 h. A final 1-h chase period was conducted with the tissue under basal (0.2-g load) or stretched (5-g load) conditions. During this final chase period, the [14C]ANF represented older, stored ANF and the [3H]ANF represented the newly synthesized peptide. After both the [14C]- and [3H]leucine pulses, immunoprecipitable isotope incorporated into ANF appeared in the chase medium within the first 10 min and stabilized to lower levels after 20 min of chase. Stretch resulted in an immediate significant increase in immunoreactive ANF release and a decrease in the medium [14C]ANF specific activity (SA). However, no change was observed in the medium [3H]ANF SA but the tissue SA tended to decrease. It is concluded that a portion of ANF is immediately and preferentially released upon synthesis, while the remainder is taken up into tissue stores and released from them at a lower rate. The secretory response to stretch was demonstrated to consist of a rapid, short-lived burst of newly synthesized ANF, suggesting an increased translocation of newly synthesized hormone into a stretch-sensitive, rapidly depletable pool. Given the nature of this pool, additional factors yet to be characterized likely come into play to maintain chronically elevated circulating levels of ANF.
Mangat
H
H
University of Ottawa Heart Institute, Ottawa Civic Hospital, Ontario, Canada.
de Bold
A J
AJ
D000818:Animals; D016275:Atrial Function; D009320:Atrial Natriuretic Factor / Q000096:biosynthesis / Q000502:physiology*; D001696:Biomechanical Phenomena; D002250:Carbon Radioisotopes; D006321:Heart / Q000502:physiology*; D007163:Immunosorbent Techniques; D066298:In Vitro Techniques; D007553:Isotope Labeling; D007700:Kinetics; D007930:Leucine / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014316:Tritium
D002250:Carbon Radioisotopes; D014316:Tritium; D009320:Atrial Natriuretic Factor; D007930:Leucine