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Evidence that epithelium‐dependent relaxation of vascular smooth muscle detected by co‐axial bioassays is not attributable to hypoxia
Author(s) -
Spina D.,
Fernandes L.B.,
Preuss J.M.H.,
Hay D.W.P.,
Muccitelli R.M.,
Page C.P.,
Goldie R.G.
Publication year - 1992
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1992.tb09060.x
Subject(s) - glibenclamide , methacholine , phenylephrine , endocrinology , medicine , histamine , endothelium derived relaxing factor , hypoxia (environmental) , aorta , chemistry , epithelium , endothelium , biology , lung , oxygen , respiratory disease , genetics , organic chemistry , blood pressure , diabetes mellitus
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 μ m ) relaxed in a time‐dependent manner ( t ½ = 8.3 ± 0.4 min, n = 38) when the bathing solution was bubbled with 95% N 2 and 5% CO 2 . In co‐axial bioassays, the t ½ for histamine (100 μ m ; guinea‐pig trachea)‐ and methacholine (100 μ 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 μ m ). In contrast, glibenclamide (100 μ m ) failed to inhibit histamine (100 μ m ; guinea‐pig trachea)‐ and methacholine (0.1–100 μ m ; rabbit bronchus)‐induced release of epithelium‐derived inhibitory factor (EpDIF), in co‐axial bioassays. Glibenclamide (100 μ 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.