title: Effects of cardiotrophin-1 on hemodynamics and endocrine function of the heart.
abstract: 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 microg/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.
authors.affiliation: Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, Japan 606-8507.
authors.forename: I
authors.initials: I
authors.lastname: Hamanaka
authors.forename: Y
authors.initials: Y
authors.lastname: Saito
authors.forename: T
authors.initials: T
authors.lastname: Nishikimi
authors.forename: T
authors.initials: T
authors.lastname: Magaribuchi
authors.forename: S
authors.initials: S
authors.lastname: Kamitani
authors.forename: K
authors.initials: K
authors.lastname: Kuwahara
authors.forename: M
authors.initials: M
authors.lastname: Ishikawa
authors.forename: Y
authors.initials: Y
authors.lastname: Miyamoto
authors.forename: M
authors.initials: M
authors.lastname: Harada
authors.forename: E
authors.initials: E
authors.lastname: Ogawa
authors.forename: N
authors.initials: N
authors.lastname: Kajiyama
authors.forename: N
authors.initials: N
authors.lastname: Takahashi
authors.forename: T
authors.initials: T
authors.lastname: Izumi
authors.forename: G
authors.initials: G
authors.lastname: Shirakami
authors.forename: K
authors.initials: K
authors.lastname: Mori
authors.forename: Y
authors.initials: Y
authors.lastname: Inobe
authors.forename: I
authors.initials: I
authors.lastname: Kishimoto
authors.forename: I
authors.initials: I
authors.lastname: Masuda
authors.forename: K
authors.initials: K
authors.lastname: Fukuda
authors.forename: K
authors.initials: K
authors.lastname: Nakao
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000201:enzymology / Q000502:physiology; D009320:Atrial Natriuretic Factor / Q000235:genetics; D002302:Cardiac Output / Q000187:drug effects; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology; D016207:Cytokines / Q000008:administration & dosage / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006131:Growth Inhibitors / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006439:Hemodynamics / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D008168:Lung / Q000201:enzymology; D008222:Lymphokines / Q000494:pharmacology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D020097:Natriuretic Peptide, Brain / Q000235:genetics; D019001:Nitric Oxide Synthase / Q000235:genetics*; D052247:Nitric Oxide Synthase Type II; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D016207:Cytokines; D006131:Growth Inhibitors; D006146:Guanidines; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines; D011994:Recombinant Proteins; D020097:Natriuretic Peptide, Brain; D009320:Atrial Natriuretic Factor; C092073:cardiotrophin 1; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; C004479:pimagedine; D019331:NG-Nitroarginine Methyl Ester