Author + information
- Adolfo J. de Bold, OC, PhD∗ ()
- Department of Pathology and Laboratory Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada
- ↵∗Reprint requests and correspondence:
Dr. Adolfo J. de Bold, University of Ottawa, Faculty of Medicine, Department of Pathology and Laboratory Medicine, 451 Smyth Road, Ottawa, Ontario K1H 8M5, Canada.
The report by Ichiki et al. (1), in this issue of JACC: Heart Failure, centers on the atrial natriuretic peptide (ANP) (ANP99–126) precursor hormone proANP (ANP1–126) and on its potential use as a therapeutic agent. Early chromatographic analysis of atrial tissue extracts clearly showed that by far, most of the natriuretic activity in these extracts was present in the high–molecular weight fractions (2). Combined with molecular cloning studies, it was demonstrated that proANP made up most of these fractions (2,3). It was later demonstrated that ANP was one of the ligands for guanylyl receptor signaling through cyclic guanosine monophosphate (4). Given these findings, Ichiki et al. (1) asked whether proANP is comparable with ANP or B-type natriuretic peptide (BNP) in some of their biological actions. To this purpose, they administered these peptides to dogs and found some significant, albeit not strikingly so, qualitative and quantitative differences between the propeptide and the other 2 peptides. Namely, proANP had greater diuretic and natriuretic properties, with more sustained renal tubular actions compared with ANP and BNP, including marked renal vasodilation, which was not observed with ANP or BNP. In addition, proANP provoked greater and more prolonged cardiac unloading than ANP but had fewer hypotensive effects than BNP. It is suggested that the greater effects of proANP compared with ANP or BNP make it an attractive molecule for further development in future therapeutic applications. Above all, these findings demonstrate the potential of higher molecular weight peptides as effective ligands for the guanylyl cyclase receptors and point the way to the use of recombinant molecules of long half-lives in the circulation, such as albumin-ANP (5) or albumin-BNP (6) in the clinic.
↵∗ Editorials published in JACC: Heart Failure reflect the views of the authors and do not necessarily represent the views of JACC: Heart Failure or the American College of Cardiology.
Dr. de Bold has reported that he has no relationships relevant to the contents of this paper to disclose.
- American College of Cardiology Foundation
- Ichiki T.,
- Huntley B.K.,
- Sangaralingham S.J.,
- Burnett J.C. Jr..
- de Bold A.J.
- Flynn T.G.,
- Davies P.L.,
- Kennedy B.P.,
- de Bold M.L.,
- de Bold A.J.