Effect of hyperoxia and metformin on vascular responses to vasoactive compounds in rats.
Exposure of cells to oxygen concentrations higher than normal (hyperoxia) damages the molecular components of cells, resulting in cellular dysfunction and death. Metformin, a biguanide molecule used for treating non-insulin-dependent diabetes, been shown to lower blood pressure. The aim of this study was to investigate the possible effects of hyperoxia and metformin on the vascular responses of thoracic aorta to vasoactive compounds, using an in vitro rat model. In the hyperoxia-control (HC) group, the response to acetylcholine was completely abolished, but metformin treatment before (MH) or after (HM) exposure to 100% oxygen restored the response to acetylcholine to near-control values. In aortas from HC, MH, or HM groups, no significant differences were found in pD2 values to the endothelium-dependent vasodilator sodium nitroprussiate. In aortic strips from metformin-treated rats, the pD2 values for noradrenaline in the presence of endothelium were significantly smaller than those in the normal control group. The maximal contractile responses to KCl were not significantly different among all experimental groups. The results of the present study show that in hyperoxia-exposed rats, metformin treatment reverses the abolished vascular relaxation to AChe.
Ozyazgan
S
S
Department of Pharmacology and Clinical Pharmacology, Cerrahpasa Faculty of Medicine, University of Istanbul, Turkey.
Ince
E
E
Senses
V
V
Sultuybek
G
G
Akkan
A G
AG
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D005260:Female; D008687:Metformin / Q000494:pharmacology*; D009599:Nitroprusside / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D010100:Oxygen / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014661:Vasoconstriction / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects*
D009599:Nitroprusside; D008687:Metformin; D000109:Acetylcholine; D010100:Oxygen; D009638:Norepinephrine