In vivo cerebrovascular effects of cocaine- and amphetamine-regulated transcript (CART) peptide

Jeffrey J. Iliff, Nabil J. Alkayed, Kiarash J. Golshani, Jason Weinstein, Richard J. Traystman, G. Alexander West

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Cocaine- and amphetamine-regulated transcript (CART) and its associated peptides have been implicated in a number of physiologic processes including modulation of the hypothalamo-pituitary-adrenal (HPA) axis and cardiovascular regulation. Recently, we reported that in isolated cerebral arterioles, CART peptide (CARTp) acts directly to produce endothelium-dependent constriction via the endothelin signaling pathway. We used the rat closed cranial window model to determine the in vivo effects of CARTp on pial arteriolar diameter. Intravenous administration of 30 μg/kg CARTp produced a significant pressor effect and constriction of pial arterioles. The pressor response to systemic CARTp was blocked by the β-adrenergic receptor antagonist propranolol (2 mg/kg IV). Direct application of 0.1 nM-1μM CARTp to pial arterioles produced a dose-dependent and long-lasting constriction to approximately 88% of baseline diameter. The constriction response to topically applied 100 nM CARTp was blocked by both the endothelin A (ETA) receptor antagonist BQ-123 (10 μM) and the inhibitor of endothelin-converting enzyme, phosphoramidon (100 nM). These results demonstrate for the first time that CARTp constricts cerebral vessels in vivo, an action mediated by its effects on the endothelin system, specifically via activation of ETA receptors. This supports the notion that CARTp plays a physiologic role in cerebrovascular regulation, particularly during times of HPA axis activation.

Original languageEnglish (US)
Pages (from-to)82-89
Number of pages8
JournalJournal of Cardiovascular Pharmacology
Volume52
Issue number1
DOIs
StatePublished - Jul 2008

Keywords

  • Cerebral blood flow
  • Cocaine- and amphetamine-regulated transcript
  • Endothelin
  • Vasoconstriction

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

Fingerprint Dive into the research topics of 'In vivo cerebrovascular effects of cocaine- and amphetamine-regulated transcript (CART) peptide'. Together they form a unique fingerprint.

  • Cite this