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Endothelium‐dependent vasorelaxation independent of nitric oxide and K + release in isolated renal arteries of rats
Author(s) -
Jiang Fan,
Dusting Gregory J
Publication year - 2001
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.0703965
Subject(s) - nitric oxide , endothelium , chemistry , blood vessel , pharmacology , biophysics , medicine , biology , organic chemistry
We investigated whether K + can act as an endothelium‐derived hyperpolarizing factor (EDHF) in isolated small renal arteries of Wistar‐Kyoto rats. Acetylcholine (0.001 – 3 μ M ) caused relaxations that were abolished by removal of the endothelium. However, acetylcholine‐induced relaxations were not affected by the nitric oxide (NO) synthase inhibitor N ω ‐nitro‐ L ‐arginine methyl ester ( L ‐NAME, 100 μ M ), by L ‐NAME plus the soluble guanylate cyclase inhibitor 1H‐[1,2,4]oxadiazolo[4,3,‐a]quinoxalin‐1‐one (ODQ, 1 μ M ) or by L ‐NAME plus the cyclo‐oxygenase inhibitor indomethacin (10 μ M ). In rings precontracted with high‐K + (60 m M ) physiological salt solution in the presence of L ‐NAME, acetylcholine‐induced relaxations were abolished.L ‐NAME‐resistant relaxations were abolished by the large‐conductance Ca 2+ ‐activated K + channel inhibitor charybdotoxin plus the small‐conductance Ca 2+ ‐activated K + channel inhibitor apamin, while the inward rectifier K + channel inhibitor Ba 2+ or the gap junction inhibitor 18α‐glycyrrhetinic acid had no effect. Acetylcholine‐induced relaxation was unchanged by ouabain (10 μ M ) but was partially inhibited by a higher concentration (100 μ M ). In half of the tissues tested, K + (10 m M ) itself produced L ‐NAME‐resistant relaxations that were blocked by ouabain (10 μ M ) and partially reduced by charybdotoxin plus apamin, but not affected by 18α‐glycyrrhetinic acid or Ba 2+ . However, K + did not induce relaxations in endothelium‐denuded tissues. In conclusion, acetylcholine‐induced relaxations in this tissue are largely dependent upon hyperpolarization mechanisms that are initiated in the endothelium but do not depend upon NO release. K + release cannot account for endothelium‐dependent relaxation and cannot be an EDHF in this artery. However, K + itself can initiate endothelium‐dependent relaxations via a different pathway from acetylcholine, but the mechanisms of K + ‐induced relaxations remain to be clarified.British Journal of Pharmacology (2001) 132 , 1558–1564; doi: 10.1038/sj.bjp.0703965