title: The chromogranin A- derived N-terminal peptide vasostatin-I: In vivo effects on cardiovascular variables in the rabbit.
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 480 μg/kg over 25 min. 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.
authors.affiliation: Dept of Neurosciences, Physiology, Medical School, Torino, Italy.
authors.forename: Silvestro
authors.initials: S
authors.lastname: Roatta
authors.forename: Magda
authors.initials: M
authors.lastname: Passatore
authors.forename: Matteo
authors.initials: M
authors.lastname: Novello
authors.forename: Barbara
authors.initials: B
authors.lastname: Colombo
authors.forename: Eleonora
authors.initials: E
authors.lastname: Dondossola
authors.forename: Mazher
authors.initials: M
authors.lastname: Mohammed
authors.forename: Gianni
authors.initials: G
authors.lastname: Losano
authors.forename: Angelo
authors.initials: A
authors.lastname: Corti
authors.forename: Karen B
authors.initials: KB
authors.lastname: Helle
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D002320:Cardiovascular Physiological Phenomena / Q000187:drug effects*; D053379:Chromogranin A / Q000097:blood / Q000494:pharmacology*; D006801:Humans; D008297:Male; D010446:Peptide Fragments / Q000097:blood / Q000494:pharmacology*; D011433:Propranolol / Q000494:pharmacology; D011817:Rabbits; D011994:Recombinant Proteins / Q000097:blood / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014661:Vasoconstriction / Q000187:drug effects*
chemical_list: D000317:Adrenergic alpha-Antagonists; D053379:Chromogranin A; D010446:Peptide Fragments; D011994:Recombinant Proteins; C064110:vasostatin I; D011433:Propranolol