期刊
JOURNAL OF EXPERIMENTAL BIOLOGY
卷 213, 期 21, 页码 3636-3643出版社
COMPANY BIOLOGISTS LTD
DOI: 10.1242/jeb.045567
关键词
chromogranin A; inotropic agents; stroke volume; myocardial relaxation; nitric oxide synthase; SERCA2a; Anguilla Anguilla L.
类别
资金
- Ministero dell'Istruzione, dell'Universita e della Ricerca
- Italian National Research Program in Antarctica (PNRA)
Catestatin (CST), the 21-amino acid, cationic and hydrophobic peptide proteolytically derived from the ubiquitous chromogranin A (CgA), is an endogenous inhibitor of catecholamine release, a potent vasodilator in vivo and an anti-hypertensive agent in mammals, including humans. Recently, we discovered that CST also functions as an important negative modulator of heart performance in frog and rat. To gain an evolutionary perspective on CST cardiotropism in fish, we analysed the influence of bovine CST (CgA(344-364)) on the eel heart, as well as the eventual species-specific mechanisms of its myocardial action. Experiments were carried out on fresh-water eels (Anguilla anguilla L.) using an electrically paced isolated working heart preparation. Stroke volume and stroke work were used as measures of ventricular performance. Under basal conditions, CST (from 11. nmol l(-1) to 165 nmol l(-1)) caused a concentration-dependent negative inotropism, which was abolished by inhibitors of either beta(1)/beta(2) (propranolol) or beta(3) (SR59230) adrenergic receptors, or by G(i/o) protein (PTx) or nitric oxide synthase (L-NMMA), or guanylate cyclase (ODQ) blockers. This suggests beta-adrenergic receptor-G(i/o) protein-NO-cGMP-dependent mechanism. By contrast, the CST-induced cardio-suppression was not influenced by atropine, unspecific muscarinic antagonist, thus excluding cholinergic receptor involvement. CST also counteracted the adrenergic (isoproterenol)-mediated positive inotropism. Under increased preload (i.e. Frank-Starling response) conditions, CST induced a significant increase of the Frank-Starling response, which was blocked by L-NMMA and thapsigargin, but independent from guanylate cyclase. In conclusion, this is the first report in fish that CST modulates myocardial performance under basal, as well as under increased preload, conditions and counteracts the adrenergic-mediated positive inotropism, which strikingly supports the evolutionary significance and establishes the cardioactive role of this peptide.
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