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Am J Physiol Heart Circ Physiol 272: H2385-H2393, 1997;
0363-6135/97 $5.00
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AJP - Heart and Circulatory Physiology, Vol 272, Issue 5 2385-H2393, Copyright © 1997 by American Physiological Society


ARTICLES

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

E. Schott, R. C. Tostes, H. San, M. Paul, R. C. Webb and E. G. Nabel
Department of Internal Medicine, University of Michigan, Ann Arbor 48109, USA.

Endothelin (ET)-1 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 cDNA (pVR-ppET) resulted in significant increase 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 (P < 0.05), in contrast to serotonin, phenylephrine, synthetic ET-1, and angiotensin II. A mitogenic effect of recombinant ET-1 on intimal 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.


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[Abstract] [Full Text] [PDF]




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