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Abstract no.: 8
Endothelium‐dependent relaxation in atherosclerotic aorta segments of apolipoprotein E‐deficient (apoE ‐/‐ ) mice
Author(s) -
Van Assche T.,
Guns P.J.,
Van Hove C.,
Herman A.G.,
Bult H.,
Fransen P.
Publication year - 2006
Publication title -
fundamental and clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.655
H-Index - 73
eISSN - 1472-8206
pISSN - 0767-3981
DOI - 10.1111/j.1472-8206.2006.00420_8.x
Subject(s) - myograph , apolipoprotein e , endocrinology , medicine , endothelium , endothelial dysfunction , phenylephrine , acetylcholine , chemistry , aorta , lesion , pathology , blood pressure , disease
The present study investigated whether lesion‐free aorta segments of young apoE ‐/‐ mice, which will later show endothelial dysfunction when atherosclerotic lesions develop, display normal endothelial function in comparison with ‘wild‐type’ (wt) C57Bl/6J mice. Endothelial function was assessed by studying endothelium‐dependent relaxation to acetylcholine (ACh) and concomitant elevations of endothelial internal calcium (Ca 2+ i ). Therefore, atherosclerosis‐prone aorta strips were mounted in a myograph with the endothelial side down and loaded with fura2‐AM (340/380 excitation emission ratio in relative units, RU) to measure Ca 2+ i simultaneously with isometric force. In 90% of WT females ( n = 10), 31% of WT males ( n = 13), 100% of apoE ‐/‐ females ( n = 14) and 82% of apoE ‐/‐ males ( n = 11), relaxation of precontracted (1 μM phenylephrine, PE) strips by ACh (2 × 10 −6 M ) was accompanied by a contemporary increase of Ca 2+ i . ACh‐induced Ca 2+ i increase was not different between WT and apoE ‐/‐ mice, but was greater in females than in males (0.14 ± 0.03 RU vs. 0.04 ± 0.03 RU, P < 0.05). Dose‐response curves for ACh (10 −9 to 3 × 10 −6 M ) revealed EC 50 ‐values for ACh‐induced relaxations, which were significantly smaller in apoE ‐/‐ than in wt (respectively 21 ± 7 nM vs. 61 ± 30 nM for females and 51 ± 22 vs. 82 ± 14 nM for males, P < 0.05), pointing to a higher sensitivity of apoE ‐/‐ segments to ACh. Except for wt males, in which relaxation seemed to be uncoupled from endothelial Ca 2+ i mobilization, EC 50 values of ACh for calcium increase were similar for the three other groups (116 ± 47, 124 ± 16 and 117 ± 7 nM, respectively). It is concluded that before development of atherosclerotic lesions, apoE ‐/‐ mice are more efficient than wt mice in transducing an increase of internal calcium upon muscarinic receptor stimulation into a nitric‐oxide dependent vasodilator response.