Vasostatin I (CgA17-76) vasoconstricts rat splanchnic vascular bed but does not affect central cardiovascular function

Ahmed A. Rahman, Israt Z. Shahid, Angelina Y. Fong, Andrew M. Hammond, Paul M. Pilowsky*

*Corresponding author for this work

Research output: Contribution to journalArticle

4 Citations (Scopus)

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 200μM, intrathecal; or 5μM, 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.

Original languageEnglish
Pages (from-to)22-28
Number of pages7
JournalAutonomic Neuroscience: Basic and Clinical
Volume166
Issue number1-2
DOIs
Publication statusPublished - 26 Jan 2012

Keywords

  • Phrenic nerve discharge
  • Rat mesenteric artery
  • Reflex
  • Sympathetic nerve activity
  • Vasostatin I

Fingerprint Dive into the research topics of 'Vasostatin I (CgA<sub>17-76</sub>) vasoconstricts rat splanchnic vascular bed but does not affect central cardiovascular function'. Together they form a unique fingerprint.

  • Cite this