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Effects of cardiotrophin-1 on hemodynamics and endocrine function of the heart
I Hamanaka1, Y Saito, T Nishikimi
1Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, Japan 606-8507.
Insights
Cardiotrophin-1 (CT-1) lowers blood pressure in rats via nitric oxide. This cytokine also boosts the expression of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) in the heart.
Area of Science:
- Cardiovascular Physiology
- Molecular Biology
- Endocrinology
Background:
- Cardiotrophin-1 (CT-1), an interleukin-6 superfamily cytokine, exhibits hypertrophic and atrial natriuretic peptide (ANP)-producing activities in vitro.
- The in vivo cardiovascular effects of CT-1 remain largely uncharacterized.
Purpose of the Study:
- To investigate the in vivo effects of Cardiotrophin-1 (CT-1) on the cardiovascular system.
- To elucidate the mechanisms underlying CT-1's cardiovascular actions.
Main Methods:
- Intravenous administration of CT-1 to conscious rats.
- Measurement of blood pressure, heart rate, and cardiac output.
- Analysis of inducible nitric oxide synthase (iNOS) mRNA expression using Northern blot and RT-PCR.
- Assessment of ANP and BNP mRNA expression in cardiac ventricles.
Main Results:
- CT-1 induced a dose-dependent decrease in blood pressure and a reflex increase in heart rate.
- CT-1 administration did not significantly alter cardiac output.
- CT-1 increased iNOS mRNA expression in the lung and aorta, which was inhibited by aminoguanidine.
- CT-1 treatment elevated ventricular expression of ANP and BNP mRNA.
Conclusions:
- CT-1 exerts a hypotensive effect in vivo through a nitric oxide-dependent pathway.
- CT-1 stimulates the expression of natriuretic peptides (ANP and BNP) in 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.