Evidence that epithelium‐dependent relaxation of vascular smooth muscle detected by co‐axial 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 μm) relaxed in a time‐dependent manner (t½ = 8.3 ± 0.4 min, n = 38) when the bathing solution was bubbled with 95% N2 and 5% CO2. In co‐axial bioassays, the t½ for histamine (100 μm; guinea‐pig trachea)‐ and methacholine (100 μm; 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 μm). In contrast, glibenclamide (100 μm) failed to inhibit histamine (100 μm; guinea‐pig trachea)‐ and methacholine (0.1–100 μm; rabbit bronchus)‐induced release of epithelium‐derived inhibitory factor (EpDIF), in co‐axial bioassays. Glibenclamide (100 μm) 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.