title: Vasostatin I (CgA17-76) vasoconstricts rat splanchnic vascular bed but does not affect central cardiovascular function.
abstract: Vasostatin I (CgA(1-76)) is a naturally occurring biologically active peptide derived from chromogranin A (CgA), and is so named for its inhibitory effects on vascular tension. CgA mRNA is expressed abundantly in sympathoexcitatory catecholaminergic neurons of the rostral ventrolateral medulla (RVLM). CgA microinjection into the RVLM decreases blood pressure (BP), heart rate (HR) and sympathetic nerve activity (SNA). Proteolytic fragments of CgA are thought to be responsible for the cardiovascular effects observed. We hypothesised that vasostatin I is one of the fragments responsible for the central effects of CgA. We examined the role of a vasostatin I fragment, CgA(17-76) (VS-I((CgA17-76))), containing the portion important for biological effects. The effects of VS-I((CgA17-76)) delivered by intrathecal injection, or microinjection into the RVLM, on cardio-respiratory function in urethane anaesthetised, vagotomised, mechanically ventilated Sprague-Dawley rats (n=21) were evaluated. The effects of intrathecal VS-I((CgA17-76)) on the somato-sympathetic, baroreceptor and peripheral chemoreceptor reflexes were also examined. At the concentrations used (10, 100 or 200 μM, intrathecal; or 5 μM, RVLM microinjection) VS-I((CgA17-76)) produced no change in mean arterial pressure, HR, splanchnic SNA, phrenic nerve amplitude or phrenic nerve frequency. All reflexes examined were unchanged following intrathecal VS-I((CgA17-76)). In the periphery, VS-I((CgA17-76)) potentiated the contractile effects of noradrenaline on rat mesenteric arteries (n=6), with a significant left-shift in the dose response curve to noradrenaline (3.7×10(-7) vs 7.7×10(-7)). Our results indicate that VS-I((CgA17-76)) is active in the periphery but not centrally, and is not a central modulator of cardiorespiratory function and physiological reflexes.
authors.affiliation: Australian School of Advanced Medicine, Macquarie University, Sydney, Australia.
authors.forename: Ahmed A
authors.initials: AA
authors.lastname: Rahman
authors.forename: Israt Z
authors.initials: IZ
authors.lastname: Shahid
authors.forename: Angelina Y
authors.initials: AY
authors.lastname: Fong
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Hammond
authors.forename: Paul M
authors.initials: PM
authors.lastname: Pilowsky
mesh_terms: D000320:Adrenergic Fibers / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D002320:Cardiovascular Physiological Phenomena / Q000187:drug effects*; D053379:Chromogranin A / Q000494:pharmacology*; D008297:Male; D008845:Microinjections / Q000379:methods; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012143:Respiratory Physiological Phenomena / Q000187:drug effects*; D013152:Splanchnic Circulation / Q000187:drug effects* / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
chemical_list: D053379:Chromogranin A; D010446:Peptide Fragments; D014662:Vasoconstrictor Agents; C064110:vasostatin I