Enhanced endothelin-mediated coronary vasoconstriction and attenuated basal nitric oxide activity in experimental

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En Face Detection of Nitric Oxide and Superoxide in Endothelial Layer of Intact Arteries
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V Mathew1, C R Cannan, V M Miller

  • 1Division of Cardiovascular Diseases and Internal Medicine, Mayo Foundation, Rochester, Minn 55905, USA.

Circulation
|October 10, 1997
PubMed

Insights

Experimental hypercholesterolemia alters coronary vasomotor responses. Endothelin-1 caused increased vasoconstriction, while nitric oxide synthase inhibition effects were reduced, indicating impaired coronary vascular reactivity.

Area of Science:

  • Cardiovascular Physiology
  • Endothelial Function
  • Metabolic Disorders

Background:

  • Experimental hypercholesterolemia is linked to coronary vasomotor dysfunction.
  • This study investigated changes in coronary vasomotor responses to endothelin and nitric oxide pathways in hypercholesterolemia.

Purpose of the Study:

  • To test the hypothesis that experimental hypercholesterolemia alters coronary vasomotor responses to endothelin and endogenous nitric oxide (NO) pathway inhibition.

Main Methods:

  • Infusion of Endothelin-1 (ET-1) and N(G)-monomethyl-L-arginine (L-NMMA) into the coronary arteries of pigs before and after a 10-week cholesterol diet.
  • Measurement of coronary blood flow (CBF), coronary artery diameter (CAD), and coronary vascular resistance (CVR).
  • Assessment of ET receptor density and immunohistochemical staining for constitutive nitric oxide synthase (NOS).

Main Results:

  • Hypercholesterolemic pigs showed significantly accentuated decreases in CBF and CAD, and increased CVR in response to ET-1.
  • The effects of L-NMMA on CBF, CAD, and CVR were attenuated in hypercholesterolemic pigs.
  • A decrease in constitutive NOS immunoreactivity was observed in the coronary arteries of hypercholesterolemic pigs.

Conclusions:

  • Experimental hypercholesterolemia enhances coronary vasoconstriction to endothelin.
  • There is an attenuated response to the inhibition of endogenous NO activity in hypercholesterolemia.
  • These findings suggest an alteration in coronary vascular reactivity in experimental hypercholesterolemia.
Abstract

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