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Lack of involvement of endothelin‐1 in angiotensin II‐induced contraction of the isolated rat tail artery
Author(s) -
Jiang Yanfen,
Triggle Christopher R
Publication year - 2000
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0703674
Subject(s) - contraction (grammar) , angiotensin ii , endocrinology , medicine , endothelin 1 , endothelin receptor , chemistry , endothelium , vascular smooth muscle , losartan , calcium , endothelins , muscle contraction , receptor , biology , smooth muscle
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. 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 μ M )‐induced a non‐sustained contraction of endothelium‐intact preparations which was not antagonized by BQ‐123 (1 μ M ), but was inhibited by losartan (10 n M ). In addition, the maximal contraction induced by ET‐1 (0.1 μ M ) could be further increased by the addition of 0.1 μ M Ang II. Ang II (0.001–0.3 μ M ) 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 m M ). Ang II did not increase [Ca 2+ ] i in endothelial cells. ET‐1 (0.1 μ M ) 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. Ang II‐induced contraction was insensitive to inhibition by nifedipine (0.1 μ M ), an antagonist of L‐type voltage‐gated Ca 2+ channels, and SK&F96365 (10 μ M ), which blocks non‐selective cation channels, whereas that to ET‐1 was inhibited by SK&F69365. 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. These results indicate that endothelium‐derived ET‐1 is not involved in the Ang II‐mediated vasoconstriction of the rat tail artery and that Ang II‐ and ET‐1‐mediated VSM contractions utilize distinct pathways.British Journal of Pharmacology (2000) 131 , 1055–1064; doi: 10.1038/sj.bjp.0703674