Possible role for K+ in endothelium-derived hyperpolarizing factor-linked dilatation in rat middle cerebral artery.

Journal article

BACKGROUND AND PURPOSE: Endothelium-derived hyperpolarizing factor (EDHF) and K+ are vasodilators in the cerebral circulation. Recently, K+ has been suggested to contribute to EDHF-mediated responses in peripheral vessels. The EDHF response to the protease-activated receptor 2 ligand SLIGRL was characterized in cerebral arteries and used to assess whether K+ contributes as an EDHF. METHODS: Rat middle cerebral arteries were mounted in either a wire or pressure myograph. Concentration-response curves to SLIGRL and K+ were constructed in the presence and absence of a variety of blocking agents. In some experiments, changes in tension and smooth muscle cell membrane potential were recorded simultaneously. RESULTS: SLIGRL (0.02 to 20 micromol/L) stimulated concentration and endothelium-dependent relaxation. In the presence of NG-nitro-L-arginine methyl ester, relaxation to SLIGRL was associated with hyperpolarization and sensitivity to a specific inhibitor of IKCa, 1-[(2-chlorophenyl)diphenylmethyl]-1H-pyrazole (1 micromol/L), reflecting activation of EDHF. Combined inhibition of KIR with Ba2+ (30 micromol/L) and Na+/K+-ATPase with ouabain (1 micromol/L) markedly attenuated the relaxation to EDHF. Raising extracellular [K+] to 15 mmol/L also stimulated smooth muscle relaxation and hyperpolarization, which was also attenuated by combined application of Ba2+ and ouabain. CONCLUSIONS: SLIGRL evokes EDHF-mediated relaxation in the rat middle cerebral artery, underpinned by hyperpolarization of the smooth muscle. The profile of blockade of EDHF-mediated hyperpolarization and relaxation supports a pivotal role for IKCa channels. Furthermore, similar inhibition of responses to EDHF and exogenous K+ with Ba2+ and ouabain suggests that K+ may contribute as an EDHF in the middle cerebral artery.

Authors: McNeish, A; Dora, K; Garland, C

• Publication status: Published
• Journal: Stroke; a journal of cerebral circulation
• Volume: 36
• Issue: 7
• Pages: 1526-1532
• Publication date: 2005-07-01
• DOI: 10.1161/01.str.0000169929.66497.73
• EISSN: 1524-4628
• ISSN: 0039-2499
• Language: English
• Keywords: Rats, Wistar; Sodium-Potassium-Exchanging ATPase; Myography; NG-Nitroarginine Methyl Ester; Receptor, PAR-2; Bradykinin; Pyrazoles; Inflammation; Barium; Potassium Channels; Cerebrovascular Circulation; Enzyme Inhibitors; Biological Factors; Pressure; Dose-Response Relationship, Drug; Animals; Ouabain; Potassium; Oligopeptides; Male; Middle Cerebral Artery; Rats