EVIDENCE THAT EPITHELIUM-DEPENDENT RELAXATION OF VASCULAR SMOOTH-MUSCLE DETECTED BY COAXIAL BIOASSAYS IS NOT ATTRIBUTABLE TO HYPOXIA

1 The present study was undertaken to examine further the contribution of hypoxia to airway epithelium-dependent relaxation of rat aorta in the co-axial bioassay. 2 Endothelium-denuded rat aorta contracted with phenylephrine (0.05-mu-M) relaxed in a time-dependent manner (t1/2 = 8.3 +/- 0.4 min, n = 38) when the bathing solution was bubbled with 95% N2 and 5% CO2. In co-axial bioassays, the t1/2 for histamine (100-mu-M; guinea-pig trachea)- and methacholine (100-mu-M; rabbit bronchus)- induced relaxation was 1.9 +/- 0.2 min (n = 14) and 1.2 +/- 0.1 min (n = 26), respectively. 3 Hypoxia-induced relaxation was not associated with a rise in intracellular guanosine 3':5'-cyclic monophosphate (cyclic GMP). This contrasts with previous findings of an elevation in cyclic GMP associated with epithelium-dependent relaxation of rat aorta in co-axial bioassays. 4 Hypoxia-induced vascular relaxation was antagonized by the ATP-sensitive K+ channel blocker, glibenclamide (100-mu-M). In contrast, glibenclamide (100-mu-M) failed to inhibit histamine (100-mu-M; guinea-pig trachea)- and methacholine (0.1-100-mu-M; rabbit bronchus)-induced release of epithelium-derived inhibitory factor (EpDIF), in co-axial bioassays. Glibenclamide (100-mu-M) antagonized BRL 38227 (lemakalin), but not isoprenaline-induced relaxation of phenylephrine-contracted rat aorta. 5 These data strongly suggest that the airway epithelium-dependent relaxant responses observed in co-axial bioassays cannot be attributed to hypoxia.