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CLINICAL RESEARCH: HEART FAILURE

Natriuretic Peptides Enhance the Production of Adiponectin in Human Adipocytes and in Patients With Chronic Heart Failure

Osamu Tsukamoto, MD, PhD^_*,, Masashi Fujita, MD, PhD, Mahoto Kato, MD^_*, Satoru Yamazaki, PhD^_*, Yoshihiro Asano, MD, PhD, Akiko Ogai, PhD^_*, Hidetoshi Okazaki, MD, PhD^_*, Mitsutoshi Asai, MD, Yoko Nagamachi, BS, Norikazu Maeda, MD, PhD, Yasunori Shintani, MD, PhD, Tetsuo Minamino, MD, PhD, Masanori Asakura, MD, PhD^_*, Ichiro Kishimoto, MD, PhD, Tohru Funahashi, MD, PhD, Hitonobu Tomoike, MD, PhD^_* and Masafumi Kitakaze, MD, PhD^_*,_*

^_* Cardiovascular Division of Medicine, National Cardiovascular Center, Suita, Osaka, Japan
Cardiovasular Division of Biochemistry, National Cardiovascular Center, Suita, Osaka, Japan
Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
Department of Metabolic Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, Japan

Manuscript received August 27, 2008; revised manuscript received January 22, 2009, accepted February 19, 2009.

^_* Reprint requests and correspondence: Dr. Masafumi Kitakaze, Department of Cardiovascular Medicine, National Cardiovascular Center, Suita, Osaka 565-8565, Japan (Email: kitakaze{at}zf6.so-net.ne.jp).

Objectives: 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 µg/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 µg/ml to 7.34 ± 0.47 µg/ml, p < 0.05), whereas there was no change of adiponectin in the saline group (from 6.53 ± 0.57 µg/ml to 6.55 ± 0.56 µg/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.

Key Words: adiponectin • natriuretic peptides • heart failure • adipose tissue

Abbreviations and Acronyms   ANP = atrial natriuretic peptide   BNP = brain natriuretic peptide   CHF = congestive heart failure   GC-A = type A guanylyl cyclase receptor   hANP = human atrial natriuretic peptide   NPR = natriuretic peptide receptor   PKG = protein kinase G

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