Characteristics of ACh‐induced hyperpolarization and relaxation in rabbit jugular vein

• Published in: British journal of pharmacology Vol. 167; no. 3; pp. 682 - 696
• Main Authors: Itoh, Takeo, Maekawa, Takashi, Shibayama, Yasushi
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.10.2012; Nature Publishing Group
• Subjects: Acetylcholine - administration & dosage; Acetylcholine - pharmacology; ACh; Animals; basal NO release; Biological and medical sciences; Calcium - metabolism; calcium‐activated K+ channels; Dose-Response Relationship, Drug; EDHF; endothelial cell hyperpolarization; Endothelium; Endothelium, Vascular - drug effects; Endothelium, Vascular - metabolism; Jugular Veins - drug effects; Jugular Veins - metabolism; Male; Medical sciences; Myocytes, Smooth Muscle - drug effects; Myocytes, Smooth Muscle - metabolism; Nitric Oxide - metabolism; Pharmacology. Drug treatments; Potassium Channels, Calcium-Activated - drug effects; Potassium Channels, Calcium-Activated - metabolism; Potassium Channels, Voltage-Gated - metabolism; rabbit jugular vein; Rabbits; Research Papers; smooth muscle cell hyperpolarization; Vasodilation - drug effects; Vasodilator Agents - administration & dosage; Vasodilator Agents - pharmacology; Veins & arteries; voltage‐dependent K+ channels; NO; Endothelial cell; smooth muscle cell hyperpolarization; Calcium; ACh; basal NO release; endothelial cell hyperpolarization; Rabbit; Smooth muscle; Ionic channel; Inorganic element; Blood vessel; Vein; Release; Lagomorpha; In vitro; Endothelium; Vertebrata; Mammalia; channels; Animal; voltage-dependent K; Circulatory system; calcium-activated K; Potassium; EDHF; Hyperpolarization; rabbit jugular vein
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1111/j.1476-5381.2012.02038.x

BACKGROUND AND PURPOSE The roles played by endothelium‐derived NO and prostacyclin and by endothelial cell hyperpolarization in ACh‐induced relaxation have been well characterized in arteries. However, the mechanisms underlying ACh‐induced relaxation in veins remain to be fully clarified. EXPERIMENTAL APPROACH ACh‐induced smooth muscle cell (SMC) hyperpolarization and relaxation were measured in endothelium‐intact and ‐denuded preparations of rabbit jugular vein. KEY RESULTS In endothelium‐intact preparations, ACh (≤10−8 M) marginally increased the intracellular concentration of Ca2+ ([Ca2+]i) in endothelial cells but did not alter the SMC membrane potential. However, ACh (10−10–10−8 M) induced a concentration‐dependent relaxation during the contraction induced by PGF2α and this relaxation was blocked by the NO synthase inhibitor Nω‐nitro‐l‐arginine. ACh (10−8–10−6 M) concentration‐dependently increased endothelial [Ca2+]i and induced SMC hyperpolarization and relaxation. These SMC responses were blocked in the combined presence of apamin [blocker of small‐conductance Ca2+‐activated K+ (SKCa, KCa2.3) channel], TRAM 34 [blocker of intermediate‐conductance Ca2+‐activated K+ (IKCa, KCa3.1) channel] and margatoxin [blocker of subfamily of voltage‐gated K+ (KV) channel, KV1]. CONCLUSIONS AND IMPLICATIONS In rabbit jugular vein, NO plays a primary role in endothelium‐dependent relaxation at very low concentrations of ACh (10−10–10−8 M). At higher concentrations, ACh (10−8−3 × 10−6 M) induces SMC hyperpolarization through activation of endothelial IKCa, KV1 and (possibly) SKCa channels and produces relaxation. These results imply that ACh regulates rabbit jugular vein tonus through activation of two endothelium‐dependent regulatory mechanisms.