Lack of involvement of endothelin-1 in angiotensin II-induced contraction of the isolated rat tail artery

Yanfen Jiang, Christopher Triggle

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5 Citations (Scopus)

Abstract

1. The contribution of endothelin-1 (ET-1) to angiotensin II (Ang II)-mediated contraction of the isolated rat tail artery was assessed with measurements of tension, and cytosolic calcium ([Ca 2+](i)). The distribution of the AT 1 receptor was studied with RT-PCR and immunohistochemistry. 2. Ang II induced an endothelium-independent contraction (pEC 50 7.95±0.06 and E(max): 0.46 g±0.05 with endothelium vs 7.81±0.02 and 0.41 g±0.07 without endothelium; P>0.05). Ang II (0.003-0.3 μM)-induced a non-sustained contraction of endothelium-intact preparations which was not antagonized by BQ-123 (1 μm), but was inhibited by losartan (10 nm). In addition, the maximal contraction induced by ET-1 (0.1 μM) could be further increased by the addition of 0.1 μM Ang II. 3. Ang II (0.001-0.3 μM) elevated [Ca 2+](i) in single vascular smooth muscle cells (VSMCs) in a dose-dependent manner (pEC 50 9.12±0.26) and the Ang II-induced increases in [Ca 2+](i) were not affected by a Ca 2+-free solution, but were abolished by pretreatment with caffeine (5 mM). Ang II did not increase [Ca 2+](i) in endothelial cells. ET-1 (0.1 μm) increased [Ca 2+](i) in single VSMCs in a normal Ca 2+ containing physiological saline solution (PSS), but not in a Ca 2+-free solution. 4. Ang II-induced contraction was insensitive to inhibition by nifedipine (0.1 μM), an antagonist of L-type voltage-gated Ca 2+ channels, and SKandF96365 (10 μM), which blocks non-selective cation channels, whereas that to ET-1 was inhibited by SKandF69365. 5. RT-PCR data indicate the expression of AT(1A) and AT(1B) on both VSMCs and endothelial cells, but immunohistochemical evidence illustrates that the AT 1 is located primarily on VSMCs. 6. These results indicate that endothelium-derived ETis not involved in the Ang II-mediated vasoconstriction of the rat tail artery and that Ang II- and ET-mediated VSM contractions utilize distinct pathways.

Original languageEnglish
Pages (from-to)1055-1064
Number of pages10
JournalBritish Journal of Pharmacology
Volume131
Issue number6
Publication statusPublished - 2000
Externally publishedYes

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Keywords

  • Angiotensin II
  • Cytosolic free Ca
  • Endothelial cell
  • Endothelin-1
  • Rat tail artery
  • Vascular smooth muscle cell
  • Vasoconstriction

ASJC Scopus subject areas

  • Pharmacology

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