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Endothelium-dependent vasorelaxation independent of nitric oxide and K(+) release in isolated renal arteries of rats.
Br J Pharmacol. 2001 Apr; 132(7):1558-64.BJ

Abstract

1. We investigated whether K(+) can act as an endothelium-derived hyperpolarizing factor (EDHF) in isolated small renal arteries of Wistar-Kyoto rats. 2. Acetylcholine (0.001 - 3 microM) 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:(omega)-nitro-L-arginine methyl ester (L-NAME, 100 microM), by L-NAME plus the soluble guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one (ODQ, 1 microM) or by L-NAME plus the cyclo-oxygenase inhibitor indomethacin (10 microM). In rings precontracted with high-K(+)(60 mM) physiological salt solution in the presence of L-NAME, acetylcholine-induced relaxations were abolished. 3. 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 18alpha-glycyrrhetinic acid had no effect. Acetylcholine-induced relaxation was unchanged by ouabain (10 microM) but was partially inhibited by a higher concentration (100 microM). 4. In half of the tissues tested, K(+)(10 mM) itself produced L-NAME-resistant relaxations that were blocked by ouabain (10 microM) and partially reduced by charybdotoxin plus apamin, but not affected by 18alpha-glycyrrhetinic acid or Ba(2+). However, K(+) did not induce relaxations in endothelium-denuded tissues. 5. 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.

Authors+Show Affiliations

Howard Florey Institute, The University of Melbourne, Victoria 3010, Australia. f.jiang@hfi.unimelb.edu.auNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

11264250

Citation

Jiang, F, and G J. Dusting. "Endothelium-dependent Vasorelaxation Independent of Nitric Oxide and K(+) Release in Isolated Renal Arteries of Rats." British Journal of Pharmacology, vol. 132, no. 7, 2001, pp. 1558-64.
Jiang F, Dusting GJ. Endothelium-dependent vasorelaxation independent of nitric oxide and K(+) release in isolated renal arteries of rats. Br J Pharmacol. 2001;132(7):1558-64.
Jiang, F., & Dusting, G. J. (2001). Endothelium-dependent vasorelaxation independent of nitric oxide and K(+) release in isolated renal arteries of rats. British Journal of Pharmacology, 132(7), 1558-64.
Jiang F, Dusting GJ. Endothelium-dependent Vasorelaxation Independent of Nitric Oxide and K(+) Release in Isolated Renal Arteries of Rats. Br J Pharmacol. 2001;132(7):1558-64. PubMed PMID: 11264250.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Endothelium-dependent vasorelaxation independent of nitric oxide and K(+) release in isolated renal arteries of rats. AU - Jiang,F, AU - Dusting,G J, PY - 2001/3/27/pubmed PY - 2001/5/18/medline PY - 2001/3/27/entrez SP - 1558 EP - 64 JF - British journal of pharmacology JO - Br J Pharmacol VL - 132 IS - 7 N2 - 1. We investigated whether K(+) can act as an endothelium-derived hyperpolarizing factor (EDHF) in isolated small renal arteries of Wistar-Kyoto rats. 2. Acetylcholine (0.001 - 3 microM) 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:(omega)-nitro-L-arginine methyl ester (L-NAME, 100 microM), by L-NAME plus the soluble guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one (ODQ, 1 microM) or by L-NAME plus the cyclo-oxygenase inhibitor indomethacin (10 microM). In rings precontracted with high-K(+)(60 mM) physiological salt solution in the presence of L-NAME, acetylcholine-induced relaxations were abolished. 3. 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 18alpha-glycyrrhetinic acid had no effect. Acetylcholine-induced relaxation was unchanged by ouabain (10 microM) but was partially inhibited by a higher concentration (100 microM). 4. In half of the tissues tested, K(+)(10 mM) itself produced L-NAME-resistant relaxations that were blocked by ouabain (10 microM) and partially reduced by charybdotoxin plus apamin, but not affected by 18alpha-glycyrrhetinic acid or Ba(2+). However, K(+) did not induce relaxations in endothelium-denuded tissues. 5. 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. SN - 0007-1188 UR - https://www.unboundmedicine.com/medline/citation/11264250/Endothelium_dependent_vasorelaxation_independent_of_nitric_oxide_and_K_+__release_in_isolated_renal_arteries_of_rats_ L2 - https://doi.org/10.1038/sj.bjp.0703965 DB - PRIME DP - Unbound Medicine ER -