Role of ET-1 receptor binding and [Ca2+]i in contraction of coronary arteries from DOCA-salt hypertensive rats

Academic Article


  • Hypertension is associated with an increase in coronary artery disease, but little is known about the regulation of coronary vascular tone by endothelin-1 (ET-1) in hypertension. The present study evaluated the mechanisms mediating altered contraction to ET-1 in coronary small arteries from deoxycorticosterone acetate (DOCA)-salt hypertensive rats. DOCA-salt rats exhibited an increase in systolic blood pressure and plasma ET-1 levels compared with placebo rats. Contraction to ET-1 (1 ×10-11 to 3 × 10-8 M), measured in isolated coronary small arteries maintained at a constant intraluminal pressure of 40 mmHg, was largely reduced in vessels from DOCA-salt rats compared with placebo rats. To determine the role of endothelin receptor binding in the impaired contraction to ET-1, 125I-labeled ET-1 receptor binding was measured in membranes isolated from coronary small arteries. Maximum binding (fmol/mg protein) and binding affinity were similar in coronary membranes from DOCA-salt rats compared with placebo rats. Changes in intracellular Ca2+ concentration ([Ca2+]i) were measured in freshly dissociated coronary small artery smooth muscle cells loaded with fura 2. ET-1 (10-9 M) produced a 30 ± 9% increase in [Ca2+]i in smooth muscle cells from placebo rats, but had no effect on cells from DOCA-salt rats (2 ± 2%). In summary, the ET-1-induced coronary artery contraction and increase in [Ca2+]i are impaired in DOCA-salt hypertensive rats, whereas endothelin receptor binding is not altered. These results suggest endothelin receptor uncoupling from signaling mechanisms and indicate that impaired [Ca2+]i signaling contributes to the decrease in ET-1-induced contraction of coronary small arteries in DOCA-salt hypertensive rats.
  • Digital Object Identifier (doi)

    Pubmed Id

  • 16079906
  • Author List

  • Giulumian AD; Molero MM; Reddy VB; Pollock JS; Pollock DM; Fuchs LC
  • Volume

  • 282
  • Issue

  • 5 51-5