Regional Differences in Anandamide- and Methanandamide- Induced Membrane Potential Changes in Rat Mesenteric Arteries

The possibility that anandamide is an endothelium-derived hy-perpolarizing factor was explored in the rat mesenteric vascu-lature by use of conventional microelectrode techniques. In the main mesenteric artery, anandamide and its more stable analog methanandamide hardly caused a measurable change in mem-brane potential of the smooth muscle cells, which promptly hyperpolarized to EDHF liberated by acetylcholine. Inhibition of endogenous anandamide breakdown by phenylmethylsulfonyl fluoride did not increase membrane responses to acetylcholine. The CB1 receptor antagonist SR141716 did not significantly influence EDHF-mediated hyperpolarization except at ex-tremely high concentrations. Smooth muscle cells of third to fourth order branches of the mesenteric artery, which have a more negative resting membrane potential and show smalle