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Agonists causing endothelium‐depndent contractions increase calcium in aortic endothelial cells of the spontaneously hypertensive rat
Author(s) -
Tang Eva HC,
Huang Yu,
So KwokFai,
Man Ricky YK,
Vanhoutte Paul M
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a289-b
Subject(s) - chemistry , acetylcholine , endocrinology , medicine , calcium , cytosol , nitric oxide , endothelium , reactive oxygen species , superoxide , agonist , ionophore , biophysics , biochemistry , biology , enzyme , receptor , organic chemistry
Experiments were designed to assess whether or not: a) the concentrations of calcium (Ca 2+ ) and reactive oxygen species (ROS) increase in endothelial cells (EC) of the rat thoracic aorta in response to the releasers of endothelium‐derived contracting factor (EDCF), acetylcholine (ACh) and the Ca 2+ ionophore A23187; and b) if so, whether or not a difference exists between spontaneously hypertensive (SHR) and normotensive (WKY) rats. Ca 2+ and ROS were measured by confocal microscopy, using Fura‐red in combination with Fluo‐4, and dichlorodihydrofluorescein diacetate, respectively. ACh and A23187 caused an instantaneous increase in cytosolic Ca 2+ concentration in EC of both SHR and WKY, which was significantly more pronounced in aortas of the former strain. The rise of Ca 2+ was not affected by indomethacin, indicating that it precedes the activation of cyclooxygenase. The rise in Ca 2+ was significantly reduced by the membrane permeable antioxidants (MnTMPyP and Peg‐catalase), indicating that antioxidants prevent agonist‐stimulated Ca 2+ overload. No stimulated bursts of ROS were detected within EC upon exposure to either ACh or A23187. These experiments suggest that the resting level of oxidants play a permissive role in the release and/or removal of Ca 2+ from the cytosol. EC of the SHR are more prone to Ca 2+ overload upon stimulation with ACh and A23187 and this abnormal accumulation of Ca 2+ is a prerequisite to initiate the activation of cyclooxygenase resulting in the production of EDCF.