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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
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*
-
NG-Nitroarginine Methyl Ester / pharmacology
-
Natriuretic Peptide, Brain / genetics
-
Nitric Oxide Synthase / genetics*
-
Nitric Oxide Synthase Type II
-
Rats
-
Rats, Wistar
-
Recombinant Proteins / administration & dosage
-
Recombinant Proteins / pharmacology
-
Reverse Transcriptase Polymerase Chain Reaction
Substances
-
Cytokines
-
Growth Inhibitors
-
Guanidines
-
Interleukin-6
-
Leukemia Inhibitory Factor
-
Lymphokines
-
Recombinant Proteins
-
Natriuretic Peptide, Brain
-
Atrial Natriuretic Factor
-
cardiotrophin 1
-
Nitric Oxide Synthase
-
Nitric Oxide Synthase Type II
-
Nos2 protein, rat
-
pimagedine
-
NG-Nitroarginine Methyl Ester