HYPOXIA REOXYGENATION SELECTIVELY IMPAIRS ALPHA(1B)-ADRENOCEPTOR FUNCTION IN SMALL MESENTERIC-ARTERIES/

The present study examined whether hypoxia/reoxygenation (H/R) attenua tes norepinephrine (NE) effectiveness in small arteries by interfering with function of alpha(1a)- and/or alpha(1b)-adrenoceptor subtypes. S mall mesenteric arteries (similar to 150 mu m) were obtained from rats mounted on a small vessel myograph in oxygenated physiological salt s olution (PSS), and the relationship between NE concentrations and cont ractile tension was assessed. Hypoxia was induced by bubbling the vess els with 95% N-2-5% 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 i nvestigate the role of reactive oxygen metabolites. In other groups, a lpha(1b)-receptors were blocked with chloroethylclonidine and alpha(1a )-receptors were blocked with 5-methylurapidil or WB-4101 to produce e xclusive alpha(1a)- or alpha(1b)-responses to NE. H/R decreased the NE negative logarithm of the mean effective concentration (pD(2): i.e., -log[EC(50)], where EC(50) is mean effective concentration) from 6.26 +/- 0.24 to 5.84 +/- 0.12 (P < 0.05). SOD and CAT prevented the H/R-in duced contractile dysfunction. alpha(1a)-Receptor responses to NE were not altered by H/R. In contrast, alpha(1b)-receptor responses were si gnificantly attenuated after H/R. The results indicate that alteration s in NE responsiveness after H/R are due-to dysfunction of the alpha(1 b) signal transduction pathway.