Endothelium-derived nitric oxide mediates the antiadrenergic effect of human vasostatin-1 in rat ventricular myocardium

Autor: Alessia Brero, Bruno Tota, Maria Pia Gallo, O Boero, Giuseppe Alloatti, Renzo Levi, Roberta Ramella
Rok vydání: 2007
Předmět:
Inotrope
Physiology
chemistry.chemical_compound
Phosphatidylinositol 3-Kinases
Myocytes
Cardiac
Cells
Cultured
Phosphoinositide-3 Kinase Inhibitors
Chromogranin A
Adrenergic beta-Agonists
Papillary Muscles
Recombinant Proteins
Endothelial stem cell
medicine.anatomical_structure
NG-Nitroarginine Methyl Ester
Circulatory system
Female
Cardiology and Cardiovascular Medicine
Wortmannin
medicine.medical_specialty
Endothelium
Calcium Channels
L-Type
Heart Ventricles
Adrenergic beta-Antagonists
Biology
Peptide hormone
In Vitro Techniques
Nitric Oxide
Nitric oxide
Contractility
Physiology (medical)
Internal medicine
medicine
Animals
Humans
Calcium Signaling
Muscle Strength
Protein Kinase Inhibitors
Dose-Response Relationship
Drug
Isoproterenol
Endothelial Cells
Myocardial Contraction
Peptide Fragments
Rats
Androstadienes
Endocrinology
chemistry
biology.protein
Cattle
Nitric Oxide Synthase
Zdroj: American journal of physiology. Heart and circulatory physiology. 292(6)
ISSN: 0363-6135
Popis: Vasostatins (VSs) are vasoactive peptides derived from chromogranin A (CgA), a protein contained in secretory granules of chromaffin and other cells. The negative inotropic effect and the reduction of isoproterenol (Iso)-dependent inotropism induced by VSs in the heart suggest that they have an antiadrenergic function. However, further investigation of the mechanisms of action of VSs is needed. The aim of the present study was to define the signaling pathways activated by VS-1 in mammalian ventricular myocardium and cultured endothelial cells that lead to the modulation of cardiac contractility. Ca2+ and nitric oxide (NO) fluorometric confocal imaging was used to study the effects induced by recombinant human VS-1 [STA-CgA-(1-76)] on contractile force, L-type Ca2+ current, and Ca2+ transients under basal conditions and after β-adrenergic stimulation in rat papillary muscles and ventricular cells and the effects on intracellular Ca2+ concentration and NO production in cultured bovine aortic endothelial (BAE-1) cells. VS-1 had no effect on basal contractility of papillary muscle, but the effect of Iso stimulation was reduced by 27%. Removal of endocardial endothelium and inhibition of NO synthesis and phosphatidylinositol 3-kinase (PI3K) activity abolished the antiadrenergic effect of VS-1 on papillary muscle. In cardiomyocytes, 10 nM VS-1 was ineffective on basal and Iso (1 μM)-stimulated L-type Ca2+ current and Ca2+ transients. In BAE-1 cells, VS-1 induced a Ca2+-independent increase in NO production that was blocked by the PI3K inhibitor wortmannin. Our results suggest that the antiadrenergic effect of VS-1 is mainly due to a PI3K-dependent NO release by endothelial cells, rather than a direct action on cardiomyocytes.
Databáze: OpenAIRE
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