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 language | English (US) |
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Pages (from-to) | H2385-H2393 |
Number of pages | 8 |
Journal | American Journal of Physiology - Heart and Circulatory Physiology |
Volume | 272 |
Issue number | 5 Pt 2 |
DOIs | |
State | Published - May 17 1997 |
Keywords
- angiotensin
- endothelin
- gene transfer
- vascular reactivity
- vasospasm
ASJC Scopus subject areas
- Physiology
- Physiology (medical)