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Propionate‐induced relaxation in rat mesenteric arteries: a role for endothelium‐derived hyperpolarising factor
Author(s) -
Knock G.,
Psaroudakis D.,
Abbot S.,
Aaronson P. I.
Publication year - 2002
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2001.013105
Subject(s) - propionate , charybdotoxin , ouabain , apamin , chemistry , endocrinology , endothelium , nitric oxide , medicine , hyperpolarization (physics) , biophysics , biochemistry , biology , sodium , stereochemistry , potassium channel , nuclear magnetic resonance spectroscopy , organic chemistry
Short chain fatty acids, including propionate, are generated in the caecum and large intestine, and when absorbed may elicit localised increases in intestinal blood flow. We sought to assess the mechanism by which propionate caused vasorelaxation. Propionate‐mediated relaxation of noradrenaline‐preconstricted rat mesenteric small arteries (RMSAs, i.d. 200–300 μm) was studied using small vessel myography. Propionate (1–30 m m ) produced a concentration‐dependent relaxation. Relaxation induced by 10 m m propionate (the approximate EC 50 ) was almost abolished by endothelial denudation, although a marked relaxation to a very high concentration of propionate (50 m m ) persisted in the absence of the endothelium. In endothelium‐intact RMSAs, relaxation to 10 m m propionate was almost abolished by elevating [K + ] o to 25 m m , but was unaffected by 100 μ m N ω ‐nitro‐ l ‐arginine methyl ester ( l ‐NAME) (68 ± 4 vs . 66 ± 3 % in controls, n = 35), or by 1 μ m indomethacin (60 ± 4 vs . 61 ± 7 % in controls, n = 15). In the presence of l ‐NAME, relaxation to 10 m m propionate was significantly and markedly (i.e. > 50 %) inhibited by 50 μ m Ba 2+ and by the combination of 100 n m charybdotoxin and 100 n m apamin. A similar effect on propionate‐mediated relaxation was also exerted by 100 μ m ouabain, and by the combination of 50 μ m barium with ouabain. Relaxation was also significantly and markedly inhibited by pre‐treatment of RMSAs with 100 n m thapsigargin or 10 μ m cyclopiazonic acid (CPA). The results demonstrate that 10 m m propionate relaxes RMSAs via endothelium‐derived hyperpolarising factor (EDHF). The observation that relaxation by propionate is inhibited by thapsigargin and CPA suggests that this action of propionate involves the release of endothelial cell Ca 2+ stores.