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Influence of vasostatins, the chromogranin A-derived peptides, on the working heart of the eel (Anguilla anguilla): negative inotropy and mechanism of action.
- Source :
-
General and comparative endocrinology [Gen Comp Endocrinol] 2004 Oct; Vol. 139 (1), pp. 20-8. - Publication Year :
- 2004
-
Abstract
- We have studied the effects of exogenous human recombinant Vasostatin-1 (VS-1), Vasostatin-2 (VS-2) and the human Chromogranin A (CGA) 7-57 synthetic peptides on the mechanical performance of the isolated and perfused working eel (Anguilla anguilla) heart. Under basal conditions, the three peptides decreased stroke volume (SV) and stroke work (SW), thus exerting negative inotropism. The VS-1-mediated negative inotropism was abolished by exposure to inhibitors of either Gi/o protein (pertussis toxin; PTx) or M1 muscarinic receptors (Pirenzepine) or calcium (Lantanum and Diltiazem) and potassium (Ba2+, 4-aminopyridine, tetraethylammonium, glibenclamide) channels, while it required an intact endocardial endothelium (EE). Using NG-monomethyl-L-arginine (L-NMMA) as an inhibitor of nitric oxide (NO) synthase (NOS), and hemoglobin as a NO scavenger, we demonstrated the obligatory role of NO signaling in mediating the vasostatin response. Pretreatment with either a specific inhibitor of soluble guanylate cyclase (GC) 1H-(1,2,4)oxadiazolo-(4,3-a)quinoxalin-1-one (ODQ), or the inhibitor of the cGMP-activated protein kinase (PKG) KT5823, abolished the VS-1-mediated inotropism, indicating the cGMP-PKG component as a crucial target of NO signaling. Of note, VS-1 was effective in counteracting the adrenergic (Isoproterenol and Phenylephrine)-mediated positive inotropism. These findings provide the first evidence that vasostatins exert cardiotropic action in fish, thus suggesting their long evolutionary history as well as their species-specific mechanisms of action.
- Subjects :
- Adrenergic Agents pharmacology
Animals
Calcium Channels physiology
Chromogranin A
Chromogranins chemical synthesis
Chromogranins chemistry
Cyclic GMP metabolism
Cyclic GMP-Dependent Protein Kinases metabolism
Endocardium physiology
Endothelium physiology
GTP-Binding Proteins physiology
Humans
In Vitro Techniques
Myocardial Contraction physiology
Nitric Oxide metabolism
Peptide Fragments chemical synthesis
Potassium Channels physiology
Receptors, Adrenergic physiology
Receptors, Cholinergic physiology
Recombinant Proteins pharmacology
Signal Transduction physiology
Stroke Volume drug effects
Anguilla physiology
Chromogranins pharmacology
Heart drug effects
Myocardial Contraction drug effects
Peptide Fragments pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 0016-6480
- Volume :
- 139
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- General and comparative endocrinology
- Publication Type :
- Academic Journal
- Accession number :
- 15474532
- Full Text :
- https://doi.org/10.1016/j.ygcen.2004.07.008