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Acta Physiologica 2010; Volume 200, Supplement 681
Abstracts of the 61st National Congress of the Italian Physiological Society
9/15/2010-9/17/2010
Varese, Italy
THE ANTI-ADRENERGIC EFFECTS EXERTED IN RAT VENTRICULAR MYOCARDIUM BY THE CHROMOGRANIN A-DERIVED PEPTIDE CATESTATIN VARIANTS ARE RELATED TO THEIR ANTI-HYPERTENSIVE POTENTIAL
Abstract number: P1
BASSINO1 E, FORNERO1 S, GALLO1 MP, CRAVERO1 D, MAHATA2 SK, TOTA3,4 B, ALLOATTI1,4 G
1Dip Biologia Animale e dellUomo, Univ. Torino, Turin, Italy
2Dept of Medicine, Univ. California and Veterans Affairs, San Diego Healthcare System, La Jolla, CA, USA
3Dip Biologia Cellulare e Dip Farmaco-Biologia, Univ. Calabria, Cosenza, Italy
4Istituto Nazionale per la Ricerca Cardiovascolare (INRC), Bologna, Italy
Catestatin (Cts) is a Chromogranin A-derived peptide with three identified human variants (G364S/P370L/R374Q-Cts) with different anti-hypertensive potential. Cts inhibits catecholamine release and reduces cardiac contractility.
Aims:
Study the action of WT-Cts and its variants on rat ventricular myocardium.
Methods:
Contractile force and Ca2+ transients were measured on papillary muscles or isolated cardiac cells (CC) in basal conditions and in the presence of b-adrenergic stimulation (ISO). NO production and eNOS phosphorylation were studied on BAE1 (Bovine Aortic Endothelial) cells. Specific blockers were used to study the role of PI3K-NO-cGMP pathway.
Results:
In basal conditions, while ineffective at 5 nM, WT-Cts transiently enhanced myocardial contractility and Ca2+ transients at higher concentrations (1050 nM). WT-Cts (550 nM) reduced the effect of ISO. The anti-adrenergic effect was not due to a direct action on CC, but mediated by a PI3K-dependent NO release from endocardial endothelial cells. Indeed, Cts induced Wortmannin-sensitive, Ca2+-independent increase of NO production and phospho-eNOS on BAE1 cells. The variant P370L-Cts, but not G364S-Cts, exerted an anti-adrenergic effect comparable to that induced by WT-Cts. Both variants, however, increased developed tension in basal conditions.
Conclusions:
Our results suggest that the anti-adrenergic effect of Cts depends on PI3K-Akt-PeNOS pathway and that its structural alterations may cause variation in potency.
To cite this abstract, please use the following information:
Acta Physiologica 2010; Volume 200, Supplement 681 :P1