Catestatin (CST), the 21-amino acid, cationic and hydrophobic peptide proteolytically derived from the ubiquitous chromograninA (CgA), is an endogenous inhibitor of catecholamine release, a potent vasodilator in vivo and an anti-hypertensive agent inmammals, including humans. Recently, we discovered that CST also functions as an important negative modulator of heartperformance in frog and rat. To gain an evolutionary perspective on CST cardiotropism in fish, we analysed the influence ofbovine CST (CgA344-364) 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 heartpreparation. Stroke volume and stroke work were used as measures of ventricular performance. Under basal conditions, CST(from 11nmoll–1to 165nmoll–1) caused a concentration-dependent negative inotropism, which was abolished by inhibitors ofeither 1/2 (propranolol) or 3 (SR59230) adrenergic receptors, or by Gi/o protein (PTx) or nitric oxide synthase (L-NMMA), orguanylate cyclase (ODQ) blockers. This suggests a -adrenergic receptor-Gi/o protein-NO-cGMP-dependent mechanism. Bycontrast, the CST-induced cardio-suppression was not influenced by atropine, unspecific muscarinic antagonist, thus excludingcholinergic receptor involvement. CST also counteracted the adrenergic (isoproterenol)-mediated positive inotropism. Underincreased 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 infish that CST modulates myocardial performance under basal, as well as under increased preload, conditions and counteracts theadrenergic-mediated positive inotropism, which strikingly supports the evolutionary significance and establishes the cardioactiverole of this peptide

The catecholamine release-inhibitory peptide catestatin (chromogranin A344-364) modulates myocardial function in fish

IMBROGNO S
;
GAROFALO F;CERRA M. C.;
2010

Abstract

Catestatin (CST), the 21-amino acid, cationic and hydrophobic peptide proteolytically derived from the ubiquitous chromograninA (CgA), is an endogenous inhibitor of catecholamine release, a potent vasodilator in vivo and an anti-hypertensive agent inmammals, including humans. Recently, we discovered that CST also functions as an important negative modulator of heartperformance in frog and rat. To gain an evolutionary perspective on CST cardiotropism in fish, we analysed the influence ofbovine CST (CgA344-364) 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 heartpreparation. Stroke volume and stroke work were used as measures of ventricular performance. Under basal conditions, CST(from 11nmoll–1to 165nmoll–1) caused a concentration-dependent negative inotropism, which was abolished by inhibitors ofeither 1/2 (propranolol) or 3 (SR59230) adrenergic receptors, or by Gi/o protein (PTx) or nitric oxide synthase (L-NMMA), orguanylate cyclase (ODQ) blockers. This suggests a -adrenergic receptor-Gi/o protein-NO-cGMP-dependent mechanism. Bycontrast, the CST-induced cardio-suppression was not influenced by atropine, unspecific muscarinic antagonist, thus excludingcholinergic receptor involvement. CST also counteracted the adrenergic (isoproterenol)-mediated positive inotropism. Underincreased 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 infish that CST modulates myocardial performance under basal, as well as under increased preload, conditions and counteracts theadrenergic-mediated positive inotropism, which strikingly supports the evolutionary significance and establishes the cardioactiverole of this peptide
chromogranin A; inotropic agents; Nitric oxide synthase
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/20.500.11770/132199
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