TY - JOUR
T1 - The chromogranin A- derived N-terminal peptide vasostatin-I: In vivo effects on cardiovascular variables in the rabbit
AU - Roatta, S
AU - Passatore, M
AU - Novello, Matteo
AU - Colombo, Barbara
AU - Dondossola, Eleonora
AU - Mohammed, Mazher
AU - Losano, Gianni
AU - Corti, Angelo
AU - Helle, Karen
PY - 2011/6/7
Y1 - 2011/6/7
N2 - 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.
AB - 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.
KW - Adrenergic blockades
KW - Conscious animal
KW - Ganglion blockade
KW - Sympathetic nervous system
KW - Vasoconstriction
KW - Vasodilatation
UR - http://www.scopus.com/inward/record.url?scp=79955648504&partnerID=8YFLogxK
U2 - 10.1016/j.regpep.2011.02.015
DO - 10.1016/j.regpep.2011.02.015
M3 - Article
VL - 168
SP - 10
EP - 20
JO - Regulatory Peptides
JF - Regulatory Peptides
SN - 0167-0115
IS - 1-3
ER -