Effects of cardiotrophin-1 on hemodynamics and endocrine function of the heart

• Published in: American journal of physiology. Heart and circulatory physiology Vol. 279; no. 1; pp. H388 - H396
• Main Authors: Hamanaka, Ichiro, Saito, Yoshihiko, Nishikimi, Toshio, Magaribuchi, Tatsuo, Kamitani, Shigeki, Kuwahara, Koichiro, Ishikawa, Masahiro, Miyamoto, Yoshihiro, Harada, Masaki, Ogawa, Emiko, Kajiyama, Noboru, Takahashi, Nobuki, Izumi, Takehiko, Shirakami, Gotaro, Mori, Kenjiro, Inobe, Yoshito, Kishimoto, Ichiro, Masuda, Izuru, Fukuda, Kazuhiko, Nakao, Kazuwa
• Format: Journal Article
• Language: English
• Published: United States 01.07.2000
• Subjects: Animals; Aorta, Thoracic - drug effects; Aorta, Thoracic - enzymology; Aorta, Thoracic - physiology; Atrial Natriuretic Factor - genetics; Cardiac Output - drug effects; Cerebral Ventricles - drug effects; Cerebral Ventricles - physiology; Cytokines - administration & dosage; Cytokines - pharmacology; Gene Expression Regulation - drug effects; Growth Inhibitors - pharmacology; Guanidines - pharmacology; Heart - drug effects; Heart - physiology; Hemodynamics - drug effects; Hemodynamics - physiology; In Vitro Techniques; Injections, Intravenous; Injections, Intraventricular; Interleukin-6; Leukemia Inhibitory Factor; Lung - enzymology; Lymphokines - pharmacology; Male; Muscle, Smooth, Vascular - drug effects; Muscle, Smooth, Vascular - enzymology; Muscle, Smooth, Vascular - physiology; Natriuretic Peptide, Brain - genetics; NG-Nitroarginine Methyl Ester - pharmacology; Nitric Oxide Synthase - genetics; Nitric Oxide Synthase Type II; Rats; Rats, Wistar; Recombinant Proteins - administration & dosage; Recombinant Proteins - pharmacology; Reverse Transcriptase Polymerase Chain Reaction
• ISSN: 0363-6135; 1522-1539
• DOI: 10.1152/ajpheart.2000.279.1.h388

1  Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, Japan 606-8507; 2  Hypertension Research Laboratory, National Cardiovascular Center Research Institute, 5-7-1 Fujishiro-dai, Suita, Osaka, Japan 565-8565; and 3  Department of Anesthesiology, Kyoto University Graduate School of Medicine, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, Japan 606-8507 Cardiotrophin-1 (CT-1), a member of the interleukin-6 superfamily of cytokines, possesses hypertrophic actions and atrial natriuretic peptide (ANP)-producing activity in vitro. The goal of our study is to elucidate whether CT-1 affects the cardiovascular system in vivo. Intravenous injection of CT-1 (4-100 µg/kg) in conscious rats evoked significant declines in blood pressure and reflex increases in heart rate (HR) in a dose-dependent manner. CT-1 induced no significant change in cardiac output (from 260.7   ± 11.0 to 264.7 ± 26.6 ml · min 1 · kg 1 , P  = not significant), which was compatible with the results from isolated perfused rat hearts; HR, change in pressure over time, left ventricular developed pressure, and perfusion pressure were unaffected. Northern blot and RT-PCR analyses revealed that CT-1 increased expression of inducible nitric oxide synthase (iNOS) in lung and aorta but not in heart or liver. Pretreatment with aminoguanidine, a specific iNOS inhibitor, inhibited both iNOS mRNA production and the depressor effect of CT-1. Interestingly, CT-1 increased ventricular expression of ANP and brain natriuretic peptide (BNP). The data demonstrate that CT-1 elicits its hypotensive effect via a nitric oxide-dependent mechanism and that CT-1 induces ANP and BNP mRNA expression in vivo. blood pressure; nitric oxide synthase; natriuretic peptide