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) |
|---|---|
| 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 |
| State | Published - May 17 1997 |
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Keywords
- angiotensin
- endothelin
- gene transfer
- vascular reactivity
- vasospasm
ASJC Scopus subject areas
- Physiology
- Physiology (medical)
Cite this
Expression of a recombinant preproendothelin-1 gene in arteries stimulates vascular contractility. / Schott, Eckart; Tostes, Rita C A; San, Hong; Paul, Martin; Clinton Webb, R.; Nabel, Elizabeth G.
In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 272, No. 5 Pt 2, 17.05.1997, p. H2385-H2393.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Expression of a recombinant preproendothelin-1 gene in arteries stimulates vascular contractility
AU - Schott, Eckart
AU - Tostes, Rita C A
AU - San, Hong
AU - Paul, Martin
AU - Clinton Webb, R.
AU - Nabel, Elizabeth G.
PY - 1997/5/17
Y1 - 1997/5/17
N2 - 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
AB - 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
KW - angiotensin
KW - endothelin
KW - gene transfer
KW - vascular reactivity
KW - vasospasm
UR - http://www.scopus.com/inward/record.url?scp=0030923098&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0030923098&partnerID=8YFLogxK
M3 - Article
VL - 272
SP - H2385-H2393
JO - American Journal of Physiology - Heart and Circulatory Physiology
JF - American Journal of Physiology - Heart and Circulatory Physiology
SN - 0363-6135
IS - 5 Pt 2
ER -