Endothelium-dependent hyperpolarization in small gastric arteries.
OBJECTIVE
In many blood vessels, stimulation of the endothelium with various vasoactive substances induces, besides the nitric oxide (NO) and prostacyclin pathways, a third mechanism evoking dilatation. It is based on hyperpolarization of the vascular smooth muscle cell membrane. In the present study, we investigated the existence of endothelium-dependent hyperpolarization in small gastric arteries of the rat and explored its underlying mechanism.


METHODS
Membrane potentials were recorded by conventional microelectrode techniques in isolated segments of small gastric arteries, the normalized diameter of which was determined from the passive wall tension-internal circumference characteristics as measured with a myograph.


RESULTS
After blocking NO and prostaglandin synthesis, application of acetylcholine (3 x 10(-7) M) resulted in a membrane hyperpolarization in endothelium intact but not in endothelium-denuded arteries. This membrane potential change was increased by pre-exposure to a low concentration (30 microM) of Ba2+, which selectively inhibits inward rectifying potassium channels. Moreover, the acetylcholine-induced hyperpolarization was unaffected by additional pre-exposure to high concentrations (0.5 mM) of the Na/K-ATPase inhibitor ouabain, which by itself caused a secondary slow endothelium-independent hyperpolarization after an initial peak depolarization.


CONCLUSIONS
We conclude that acetylcholine produces endothelium-dependent hyperpolarization in gastric small arteries, which does not rely on activation of smooth muscle cell inward rectifying K+ channels or Na/K pumps, and might prove to be another important regulator of gastric mucosal blood flow.
Vanheel
B
B
Department of Physiology and Physiopathology, Gent University, U.Z.-Blok B, De Pintelaan 185, Ghent B-9000, Belgium. bert.vanheel@ugent.be
Breyne
J
J
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D001158:Arteries; D001464:Barium / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects*; D005260:Female; D008564:Membrane Potentials; D010042:Ouabain / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow / Q000187:drug effects; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors; D013270:Stomach / Q000098:blood supply*
D001464:Barium; D010042:Ouabain; D000254:Sodium-Potassium-Exchanging ATPase; D000109:Acetylcholine