Expression of a recombinant preproendothelin-1 gene in arteries stimulates vascular contractility

Eckart Schott, Rita C A Tostes, Hong San, Martin Paul, R. Clinton Webb, Elizabeth G. Nabel

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Endothelin (ET)-l is a potent vasoconstrictor peptide that is elevated in cardiovascular diseases. However, the biological function of ET-1 gene expression within arteries in vivo has not been determined. The effects of ET-1 gene expression were investigated using gene-transfer methods on porcine vascular cells in vitro and porcine arteries in vivo. Transfection of vascular cells with a vector encoding for human preproendothelin-1 cDNA1 (pVR-ppET) resulted in significant increases in active ET-1 levels in culture supernatant compared with nontransfected cells (P < 0.05). This supernatant contracted rat aortic strips at concentrations 10-fold lower than synthetic ET-1 protein,. which was inhibited by the ET-A receptor antagonist BQ-123. Transfection of pVR-ppET into pig iliofemoral arteries resulted in an increase in contractile responses to angiotensin I compared with control vessels (Px< 0.05),'în contrast to serotonin, phenylephrine, synthetic ET-1, and angiotensin II. Amitogenic effect of recombinant ET-1 on intimai cell growth was not observed. These findings demonstrate that expression of a recombinant ET-1 gene in vivo augments vascular contractility due to an increased sensitivity to angiotensin I, suggesting a role for ET-1 in the pathogenesis of cardiovascular diseases. endothelin; angiotensin; gene transfer; vascular reactivity; vasospasm

Original languageEnglish (US)
Pages (from-to)H2385-H2393
Number of pages8
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume272
Issue number5 Pt 2
DOIs
StatePublished - May 17 1997

Keywords

  • angiotensin
  • endothelin
  • gene transfer
  • vascular reactivity
  • vasospasm

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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