Chromogranin A N-terminal fragments vasostatin-1 and the synthetic CGA 7-57 peptide act as cardiostatins on the isolated working frog heart

Angelo Corti, Cinzia Mannarino, Rosa Mazza, Tommaso Angelone, Renato Longhi, Bruno Tota

Research output: Contribution to journalArticle

Abstract

Chromogranin A (CGA) N-terminal fragments corresponding to residues 1-76 and 1-113, named vasostatins for their inhibitory effects on vascular tension, have been postulated as important homeostatic regulators of the cardiovascular system. We have used an in vitro isolated working frog (Rana esculenta) heart as a bioassay to study the effects of exogenous human recombinant CGA 1-76 (VS-1) and human CGA 7-57 synthetic peptide on cardiac performance. Under basal conditions, the concentration-response curves of the two peptides exhibited a significant negative inotropism. This vasostatin response was unaffected by pretreatment with either Triton X-100 or two nitric oxide synthase inhibitors, i.e., NG-monomethyl-L-arginine and L-N5(1-iminoethyl) ornithine or the soluble guanylate cyclase inhibitor 1H-(1,2,4) oxadiazolo-(4,3-a) quinoxalin-1-one, indicating an endocardial endothelium-nitric oxide-cGMP-independent mechanism. The negative inotropism was also unaffected by either adrenergic (i.e., phentolamine and propranolol) or muscarinic (atropine) receptor or G proteins (pertussis toxin) inhibition. On the contrary, it was dependent from both extracellular Ca2+ and K+ channels, since it was abolished by pretreatment to either the Ca2+ channel inhibitors lanthanum and diltiazem or the K+ channel inhibitors Ba2+, 4-aminopyridine, tetraethylammonium chloride, and glibenclamide. In conclusion, the findings that vasostatins exert an inhibitory modulation on basal cardiac performance and counteract, as previously reported, the adrenergic-mediated positive inotropism, strongly support a cardio-regulatory role for these peptides.

Original languageEnglish
Pages (from-to)217-224
Number of pages8
JournalGeneral and Comparative Endocrinology
Volume136
Issue number2
DOIs
Publication statusPublished - Apr 2004

Keywords

  • Cardioactive peptides
  • Catecholamines
  • Chromaffin granules
  • Frog heart
  • Myocardial modulation
  • Potassium channels

ASJC Scopus subject areas

  • Endocrinology

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