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

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 mu g/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 mu g/ml (200 nM) before onset of vascular effects and declined rapidly to similar 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 a-adrenergic blocker a long lasting vasodilatation, unaffected by propranolol, was apparent on both innervated and decentralized sides. In conclusion, VS-1 induced an alpha-adrenoceptor-mediated vasoconstriction presumably brought about by noradrenaline release from sympathetic nerves when infused at a dose giving an initial serum concentration of similar to 200 nM. This initial vasoconstriction masked a persistent adrenoceptor-independent vasodilatation, consistent with previous reports from in vitro models. (C) 2011 Elsevier B.V. All rights reserved.