Circulating and tissue endothelin immunoreactivity in hypercholesterolemic pigs

Amir Lerman, Mark W I Webster, James H. Chesebro, William D. Edwards, Chi Ming Wei, Valentin Fuster, John C Jr. Burnett

Research output: Contribution to journalArticle

137 Citations (Scopus)

Abstract

Background. Hypercholesterolemia is characterized by a coronary vasoconstrictive response to the endothelium-dependent vasodilator acetylcholine. This abnormality may be due to reduced synthesis of endothelium-derived relaxing factor and/or enhanced synthesis and release of an endothelium-derived contracting factor. Endothelin is an endothelium-derived vasoconstrictor and mitogenic peptide that is present in normal plasma, and its circulating concentrations are elevated in disease states that are characterized by abnormal endothelium-dependent relaxation to acetylcholine. The current studies were designed to test the hypotheses that experimental hypercholesterolemia results in elevation of plasma and tissue endothelin immunoreactivity and that the abnormal acetylcholine-evoked coronary vasoconstriction in the hypercholesterolemic animals is associated with further elevation of plasma endothelin. Methods and Results. Plasma concentrations and molecular forms of endothelin immunoreactivity were determined following 2% cholesterol diet for 4 months in pigs and during intracoronary acetylcholine administration. Second, we assessed the presence of endothelin in the coronary vascular wall by using immunohistochemistry. Hypercholesterolemia elevated plasma endothelin concentration and enhanced coronary artery tissue endothelin immunoreactivity. The endothelium-dependent vasodilator acetylcholine further increases plasma endothelin in hypercholesterolemia in association with coronary vasoconstriction. The predominant molecular form of endothelin in hypercholesterolemia is the biological active endothelin-1. Conclusions. This study suggests a role for endothelin as an early participant and a marker for the endothelial dysfunction in hypercholesterolemia as well as a participant in the atherogenic process.

Original languageEnglish (US)
Pages (from-to)2923-2928
Number of pages6
JournalCirculation
Volume88
Issue number6
StatePublished - Dec 1993

Fingerprint

Endothelins
Swine
Hypercholesterolemia
Acetylcholine
Endothelium-Dependent Relaxing Factors
Endothelium
Vasoconstriction
Vasoconstrictor Agents
Endothelin-1
Blood Vessels
Coronary Vessels
Immunohistochemistry
Cholesterol
Diet
Peptides

Keywords

  • Cholesterol
  • Coronary
  • Endothelin
  • Relaxing factors

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Lerman, A., Webster, M. W. I., Chesebro, J. H., Edwards, W. D., Wei, C. M., Fuster, V., & Burnett, J. C. J. (1993). Circulating and tissue endothelin immunoreactivity in hypercholesterolemic pigs. Circulation, 88(6), 2923-2928.

Circulating and tissue endothelin immunoreactivity in hypercholesterolemic pigs. / Lerman, Amir; Webster, Mark W I; Chesebro, James H.; Edwards, William D.; Wei, Chi Ming; Fuster, Valentin; Burnett, John C Jr.

In: Circulation, Vol. 88, No. 6, 12.1993, p. 2923-2928.

Research output: Contribution to journalArticle

Lerman, A, Webster, MWI, Chesebro, JH, Edwards, WD, Wei, CM, Fuster, V & Burnett, JCJ 1993, 'Circulating and tissue endothelin immunoreactivity in hypercholesterolemic pigs', Circulation, vol. 88, no. 6, pp. 2923-2928.
Lerman A, Webster MWI, Chesebro JH, Edwards WD, Wei CM, Fuster V et al. Circulating and tissue endothelin immunoreactivity in hypercholesterolemic pigs. Circulation. 1993 Dec;88(6):2923-2928.
Lerman, Amir ; Webster, Mark W I ; Chesebro, James H. ; Edwards, William D. ; Wei, Chi Ming ; Fuster, Valentin ; Burnett, John C Jr. / Circulating and tissue endothelin immunoreactivity in hypercholesterolemic pigs. In: Circulation. 1993 ; Vol. 88, No. 6. pp. 2923-2928.
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