Hypoxia/reoxygenation selectively impairs alpha 1b-adrenoceptor function in small mesenteric arteries.
The present study examined whether hypoxia/reoxygenation (H/R) attenuates norepinephrine (NE) effectiveness in small arteries by interfering with function of alpha 1a- and/or alpha 1b- adrenoceptor subtypes. Small mesenteric arteries (approximately 150 microns) were obtained from rats mounted on a small vessel myograph in oxygenated physiological salt solution (PSS), and the relationship between NE concentrations and contractile tension was assessed. Hypoxia was induced by bubbling the vessels with 95% N2-5% CO2 for 15 min. Vessels were then reoxygenated for 30 min, and NE responses were reevaluated. Superoxide dismutase (SOD) and catalase (CAT) were added to the PSS in one group of vessels to investigate the role of reactive oxygen metabolites. In other groups, alpha 1b-receptors were blocked with chloroethylclonidine and alpha 1a-receptors were blocked with 5-methylurapidil or WB-4101 to produce exclusive alpha 1a- or alpha 1b-responses to NE. H/R decreased the NE negative logarithm of the mean effective concentration (pD2: i.e., -log[EC50], where EC50 is mean effective concentration) from 6.26 +/- 0.24 to 5.84 +/- 0.12 (P < 0.05). SOD and CAT prevented the H/R-induced contractile dysfunction. alpha 1a-Receptor responses to NE were not altered by H/R. In contrast, alpha 1b-receptor responses were significantly attenuated after H/R. The results indicate that alterations in NE responsiveness after H/R are due to dysfunction of the alpha 1b signal transduction pathway.
Gao
H
H
Department of Physiology, Louisiana State University Medical Center, Shreveport 71130-3932, USA.
Korthuis
R J
RJ
Benoit
J N
JN
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000332:Aerobiosis; D000818:Animals; D002374:Catalase / Q000494:pharmacology; D003000:Clonidine / Q000031:analogs & derivatives / Q000494:pharmacology; D004146:Dioxanes / Q000494:pharmacology; D000860:Hypoxia; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000502:physiology*; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects / Q000502:physiology*; D013482:Superoxide Dismutase / Q000494:pharmacology; D015016:Yohimbine / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D004146:Dioxanes; D010879:Piperazines; D018340:Receptors, Adrenergic, alpha-1; C057446:5-methylurapidil; D015016:Yohimbine; C051731:chlorethylclonidine; D011433:Propranolol; C010654:(2-(2',6'-dimethoxy)phenoxyethylamino)methylbenzo-1,4-dioxane; D002374:Catalase; D013482:Superoxide Dismutase; D003000:Clonidine; D009638:Norepinephrine