Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
9012929 | Life Sciences | 2005 | 8 Pages |
Abstract
The effects of high glucose on endothelium-derived hyperpolarizing factor (EDHF)-mediated relaxations of isolated rat mesenteric artery and the possible involvement of reactive oxygen species in these responses were investigated. After precontraction with phenylephrine (3 Ã 10â 8-10â 7 M), acetylcholine (10â 8-3 Ã 10â 6 M) and A 23187 (10â 8-3 Ã 10â 6 M), a calcium ionophore, induced concentration-dependent relaxations in the presence of NW-nitro-l-arginine methyl ester (L-NAME) (10â 4 M) and indomethacin (10â 5 M). These relaxations were abolished in the presence of charybdotoxin (2 Ã 10â 7 M) plus apamin (10â 7 M) and were assumed to be mediated by EDHF. Effects of elevated glucose were examined by incubating the arterial rings for 6 h in Krebs-Henseleit solution containing 22.2 mM glucose. Under these conditions relaxation to acetylcholine was significantly attenuated but was unchanged when the tissues were incubated for 6 h in solution containing 11.1 mM mannitol used as hyperosmotic control. Addition of superoxide dismutase (SOD) (75 U/ml) and combination of SOD with catalase (200 U/ml) during incubation with high glucose significantly preserved the impairment of EDHF-mediated relaxations to acetylcholine. A 23187-induced endothelium-dependent relaxation was not affected by high glucose. Similarly, relaxations to pinacidil (10â 10-10â 5 M) and to sodium nitroprusside (SNP) (10â 10-3 Ã 10â 7 M) were also unchanged in the rings exposed to high glucose. These results suggest that in rat mesenteric arteries exposed to elevated glucose receptor-dependent EDHF-mediated relaxations (acetylcholine-induced) are impaired whereas receptor-independent ones (A 23187-induced) and responses to smooth muscle relaxants that exert their effects through mechanisms independent of endothelium are unaffected. Our findings lead us to propose that reactive oxygen species like superoxide (·O2â) and hydrogen peroxide (H2O2) do seem to play a role in the impairment of EDHF-mediated relaxations in the presence of elevated glucose.
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Authors
Melike Hacer Ãzkan, Serdar Uma,