Glycyrrhetinic acid-sensitive mechanism does not make a major contribution to non-prostanoid, non-nitric oxide mediated endothelium-dependent relaxation of rat mesenteric artery in response to acetylcholine.

Pharmacological characteristics of non-prostanoid (PGI2), non-NO mediated endothelium-dependent relaxation in response to acetylcholine (ACh) were examined in the isolated rat mesenteric artery, especially focusing on the possible contribution of the gap junctional communication in the response. ACh produced an endothelium-dependent relaxation of the isolated rat mesenteric artery with functional endothelium in the presence of both indomethacin (3 x 10(-6) M) and N(G)-nitro-L-arginine methyl ester (L-NAME) (10(-4) M), an inhibitor of nitric oxide synthase (NOS). ACh-induced relaxation of the rat mesenteric artery in the presence of indomethacin and L-NAME was strongly attenuated in the solution containing high (80 mM) KCl, tetraethylammonium (TEA) (10(-2) M), which suggests the involvement of endothelium-derived relaxing factor(s) (EDHF(s)) in the response. Non-PGI2, non-NO mediated endothelium-dependent relaxation to ACh was not profoundly affected by glibenclamide (10(-6) M), 4-aminopyridine (4-AP) (10(-4) M), iberiotoxin (10(-7) M), agitoxin-2 (10(-8) M), or apamin (10(-7) M), but was abolished by the treatment with apamin (10(-7) M) plus charybdotoxin (10(-7) M). Non-PGI2, non-NO mediated endothelium-dependent relaxation to ACh was not substantially affected by arachidonic acid (AA) (10(-4) M) or ONO-RS-082 (10(-5) M), an inhibitor of phospholipase A2, which rules out the involvement of AA metabolites in the vascular response. Furthermore, a gap junction inhibitor, 18alpha-glycyrrhetinic acid (18alpha-GA) did not show dramatic inhibitory effect on non-PGI2, non-NO mediated endothelium-dependent relaxation induced by ACh. These findings suggest that 1) metabolites of AA are not involved in non-PGI2, non-NO mediated endothelium-dependent relaxation to ACh in the isolated rat mesenteric artery; 2) Heterocellular gap junctional communication does not mainly account for non-PGI2, non-NO mediated endothelium-dependent relaxation evoked by ACh in this artery.