Expression of C-type natriuretic peptide and of its receptor NPR-B in normal and failing heart.
C-type natriuretic peptide (CNP) was recently found in the myocardium, but possible insights into differences between atrium and ventricle production are so far lacking. Our aim was to evaluate, in an experimental model of pacing-induced heart failure (HF), plasma and tissue levels of CNP and mRNA expression of the peptide and of its specific receptor, NPR-B. Cardiac tissue was collected from male adult minipigs without (control, n=5) and with pacing-induced HF (n=5). Blood samples were collected at baseline and after pacing (10 min, 1, 2, 3 weeks). CNP in plasma and in cardiac extracts was determined by a radioimmunoassay, while the expression of mRNA by real time PCR. Compared to control, plasma CNP was increased after 1 week of pacing stress (36.9+/-10.4 pg/ml vs.16.7+/-1.1, p=0.013, mean+/-S.E.M.). As to myocardial extract, at baseline, CNP was found in all cardiac chambers and its content was 10-fold higher in atria than in ventricles (RA: 13.7+/-1.9 pg/mg protein; LA: 8.7+/-3.8; RV: 1.07+/-0.33; LV: 0.93+/-0.17). At 3 weeks of pacing, myocardial levels of CNP in left ventricle were higher than in controls (15.8+/-9.9 pg/mg protein vs. 0.9+/-0.17, p=0.01). CNP gene expression was observed in controls and at 3 weeks of pacing. NPR-B gene expression was found in all cardiac regions analyzed, and a down-regulation was observed in ventricles after HF. The co-localization of the CNP system and NPR-B suggests a possible role of CNP in HF and may prompt novel therapeutical strategies.
CNR Institute of Clinical Physiology and Fondazione G. Monasterio, Laboratory of Cardiovascular Biochemistry, Pisa, Italy. delry@ifc.cnr.it
Silvia
S
Del Ry
Manuela
M
Cabiati
Vincenzo
V
Lionetti
Michele
M
Emdin
Fabio A
FA
Recchia
Daniela
D
Giannessi
D000818:Animals; D002304:Cardiac Pacing, Artificial / Q000379:methods; D006333:Heart Failure / Q000378:metabolism*; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D020098:Natriuretic Peptide, C-Type / Q000096:biosynthesis*; D017461:Receptors, Atrial Natriuretic Factor / Q000096:biosynthesis*; D013552:Swine; D013556:Swine, Miniature; D000099242:Atrial Natriuretic Factor Receptor B
D020098:Natriuretic Peptide, C-Type; D017461:Receptors, Atrial Natriuretic Factor; D000099242:Atrial Natriuretic Factor Receptor B