The chromogranin A- derived N-terminal peptide vasostatin-I: In vivo effects on cardiovascular variables in the rabbit

Silvestro Roatta, Magda Passatore, Matteo Novello, Barbara Colombo, Eleonora Dondossola, Mazher Mohammed, Gianni Losano, Angelo Corti, Karen B. Helle

Research output: Contribution to journalArticlepeer-review

Abstract

This study is the first to report on vascular effect of the chromogranin A derived Vasostatin-I (CgA 1-76) in vivo. Cardiovascular parameters were recorded in 29 rabbits with sympathetically decentralized right carotid vascular bed. The recombinant human STA CgA 1-78 (VS-1) was infused at 480μg/kg over 25min. Group I was kept awake while groups II-V were anesthetized with Ketamine-xylazine. VS-1 was given alone in groups I-II while in presence of either phentolamine, phentolamine plus propranolol or hexamethonium in groups III-V.Serum VS-1 peaked at 2. μg/ml (200 nM) before onset of vascular effects and declined rapidly to ~. 200 ng/ml within 30 min. In all groups but III and IV VS-1 induced a brief vasoconstriction, being larger in intact than in sympathetically decentralized beds. The VS-1 induced vasoconstriction was not altered by hexamethonium but was abolished by phentolamine. In presence of the α-adrenergic blocker a long lasting vasodilatation, unaffected by propranolol, was apparent on both innervated and decentralized sides.In conclusion, VS-1 induced an α-adrenoceptor-mediated vasoconstriction presumably brought about by noradrenaline release from sympathetic nerves when infused at a dose giving an initial serum concentration of ~. 200 nM. This initial vasoconstriction masked a persistent adrenoceptor-independent vasodilatation, consistent with previous reports from in vitro models.

Original languageEnglish
Pages (from-to)10-20
Number of pages11
JournalRegulatory Peptides
Volume168
Issue number1-3
DOIs
Publication statusPublished - Jun 7 2011

Keywords

  • Adrenergic blockades
  • Conscious animal
  • Ganglion blockade
  • Sympathetic nervous system
  • Vasoconstriction
  • Vasodilatation

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Endocrinology
  • Physiology
  • Cellular and Molecular Neuroscience

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