Natriuretic peptides enhance the production of adiponectin in human adipocytes and in patients with chronic heart failure.
OBJECTIVE
We investigated the functional relationship between natriuretic peptides and adiponectin by performing both experimental and clinical studies.


BACKGROUND
Natriuretic peptides are promising candidates for the treatment of congestive heart failure (CHF) because of their wide range of beneficial effects on the cardiovascular system. Adiponectin is a cytokine derived from adipose tissue with various cardiovascular-protective effects that has been reported to show a positive association with plasma brain natriuretic peptide (BNP) levels in patients with heart failure.


METHODS
The expression of adiponectin messenger ribonucleic acid (mRNA) and its secretion were examined after atrial natriuretic peptide (ANP) or BNP was added to primary cultures of human adipocytes in the presence or absence of HS142-1 (a functional type A guanylyl cyclase receptor antagonist). Changes of the plasma adiponectin level were determined in 30 patients with CHF who were randomized to receive intravenous ANP (0.025 microg/kg/min human ANP for 3 days, n = 15) or saline (n = 15).


RESULTS
Both ANP and BNP dose-dependently enhanced the expression of adiponectin mRNA and its secretion, whereas such enhancement was inhibited by pre-treatment with HS142-1. The plasma adiponectin level was increased at 4 days after administration of human ANP compared with the baseline value (from 6.56 +/- 0.40 microg/ml to 7.34 +/- 0.47 microg/ml, p < 0.05), whereas there was no change of adiponectin in the saline group (from 6.53 +/- 0.57 microg/ml to 6.55 +/- 0.56 microg/ml).


CONCLUSIONS
Natriuretic peptides enhance adiponectin production by human adipocytes in vitro and even in patients with CHF, which might have a beneficial effect on cardiomyocytes in patients receiving recombinant natriuretic peptide therapy for heart failure.
Tsukamoto
Osamu
O
Cardiovascular Division of Medicine, National Cardiovascular Center, Suita, Osaka, Japan.
Fujita
Masashi
M
Kato
Mahoto
M
Yamazaki
Satoru
S
Asano
Yoshihiro
Y
Ogai
Akiko
A
Okazaki
Hidetoshi
H
Asai
Mitsutoshi
M
Nagamachi
Yoko
Y
Maeda
Norikazu
N
Shintani
Yasunori
Y
Minamino
Tetsuo
T
Asakura
Masanori
M
Kishimoto
Ichiro
I
Funahashi
Tohru
T
Tomoike
Hitonobu
H
Kitakaze
Masafumi
M
D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D052242:Adiponectin / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D000328:Adult; D009320:Atrial Natriuretic Factor / Q000627:therapeutic use; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005260:Female; D006333:Heart Failure / Q000097:blood / Q000188:drug therapy / Q000378:metabolism*; D006801:Humans; D008875:Middle Aged; D045283:Natriuretic Agents / Q000627:therapeutic use; D045265:Natriuretic Peptides / Q000235:genetics / Q000494:pharmacology*; D011446:Prospective Studies; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology
D052242:Adiponectin; D045283:Natriuretic Agents; D045265:Natriuretic Peptides; D012333:RNA, Messenger; D011994:Recombinant Proteins; D009320:Atrial Natriuretic Factor