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Nitric oxide‐dependent relaxation is modulated by intermediate conductance Ca2+‐activated potassium channels in rat mesenteric resistance arteries
Author(s) -
Baserman Jason N,
Kerr Paul M,
Cole William C,
Plane Frances
Publication year - 2007
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.21.6.a1230-d
Subject(s) - apamin , mesenteric arteries , chemistry , endothelium derived hyperpolarizing factor , hyperpolarization (physics) , acetylcholine , iberiotoxin , phenylephrine , nitric oxide , potassium channel , endocrinology , vasodilation , calcium activated potassium channel , medicine , biophysics , anesthesia , charybdotoxin , artery , biology , stereochemistry , blood pressure , nuclear magnetic resonance spectroscopy
Endothelium‐dependent relaxation of isolated rat mesenteric resistance arteries to acetylcholine (ACh) is mediated by the release of nitric oxide (NO) and by endothelium‐dependent hyperpolarization. We have investigated the role of Ca 2+ ‐activated potassium channels (K Ca ) in NO‐mediated, endothelium‐dependent relaxation of mesenteric resistance arteries. Pre‐incubation with either 1‐[(2‐chlorophenyl) diphenylmethyl]‐1H‐pyrazole (Tram‐34; 5 μM), an inhibitor of intermediate conductance K Ca (IK Ca ), or L‐N G ‐nitroarginine methylester (L‐NAME; 100 μM), an inhibitor of NO synthase, caused significant inhibition of relaxation to ACh in arterial segments pre‐contracted with phenylephrine (1–3 μM). The magnitude of inhibition caused by Tram‐34 was not significantly different from that caused by L‐NAME and the effects of the two inhibitors were not additive. Pre‐incubation with apamin (50 nM), an inhibitor of small conductance K Ca , did not significantly alter ACh‐evoked relaxation. However, in the presence of L‐NAME, apamin significantly inhibited relaxations to ACh and the combination of apamin with Tram‐34 reduced the maximum relaxation to ACh by 80%. Addition of L‐NAME with apamin and Tram‐34 did not cause further significant inhibition. Tram‐34 and apamin were without effect on relaxations evoked by the NO donor diethylamine NONOate. These data indicate that endothelial IK Ca play a key role modulating NO‐dependent relaxation to ACh in rat mesenteric resistance arteries. Supported by Heart & Stroke Foundation of Canada, URGC & USRP.