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

S Roatta, M Passatore, Matteo Novello, Barbara Colombo, Eleonora Dondossola, Mazher Mohammed, Gianni Losano, Angelo Corti, Karen Helle

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    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 - 7 Jun 2011

    Keywords

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

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