The interaction between endothelin-1 and nitric oxide in the vasculature: new perspectives

  • Stephane L. Bourque
    Department of Obstetrics and Gynaecology, University of Alberta, Edmonton, Alberta; and
  • Sandra T. Davidge
    Department of Obstetrics and Gynaecology, University of Alberta, Edmonton, Alberta; and
  • Michael A. Adams
    Department of Pharmacology and Toxicology, Queen's University, Kingston, Ontario, Canada

説明

<jats:p>Nitric oxide (NO) and endothelin-1 (ET-1) are natural counterparts in vascular function, and it is becoming increasingly clear that an imbalance between these two mediators is a characteristic of endothelial dysfunction and is important in the progression of vascular disease. Here, we review classical and more recent data that suggest that ET-1 should be regarded as an essential component of NO signaling. In particular, we review evidence of the role of ET-1 in models of acute and chronic NO synthase blockade. Furthermore, we discuss the possible mechanisms by which NO modulates ET-1 activity. On the basis of these studies, we suggest that NO tonically inhibits ET-1 function, and in conditions of diminished NO bioavailability, the deleterious effects of unmitigated ET-1 actions result in vasoconstriction and eventually lead to vascular remodeling and dysfunction.</jats:p>

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