title: Effects of basal and acetylcholine-induced release of endothelium-derived relaxing factor on contraction to alpha-adrenoceptor agonists in a rabbit artery and corresponding veins.
abstract: 1. The effects of an endothelium-dependent (acetylcholine) and an endothelium-independent (sodium nitroprusside) relaxant against noradrenaline-induced contractions were compared in three isolated superficial blood vessels of the rabbit, the lateral saphenous vein, plantaris vein and distal saphenous artery. Both produced concentration-related relaxations of all three vessels and were more effective against submaximal than maximal contractions to noradrenaline. Transient contractions to high concentration of acetylcholine occurred only in endothelium-intact preparations of saphenous vein and were inhibited by flurbiprofen. 2. In endothelium-denuded preparations sodium nitroprusside was 3 times more effective than in endothelium-intact preparations, while acetylcholine (less than 3 microM) was inactive. Sensitivity was similar for each relaxant: lateral saphenous vein greater than or equal to plantaris vein greater than distal saphenous artery. The similar profile of sodium nitroprusside and acetylcholine suggests that differences in susceptibility to endothelium-derived relaxing factor (EDRF) are caused by inter-vessel variations in the excitation-coupling process for noradrenaline. 3. Haemoglobin inhibited acetylcholine-induced relaxations in the endothelium-intact preparation of the lateral saphenous vein and distal saphenous artery, which suggests a similar EDRF in each preparation and the likelihood that this is a single substance, presumably nitric oxide. 4. The influence of basal, spontaneously released EDRF on alpha-adrenoceptor function was tested either by mechanical disruption of the endothelium or by adding haemoglobin to endothelium-intact segments. Endothelial disruption slightly reduced contractions to noradrenaline (NA) in distal saphenous artery but increased response size of lateral saphenous and plantaris veins, in the latter also increasing sensitivity to NA: haemoglobin mimicked endothelial disruption. Thus, basal release of EDRF like acetylcholine and nitroprusside was more effective in the veins than in the corresponding artery. 5. In lateral saphenous vein responses to phenylephrine were enhanced by endothelial disruption, but without change in sensitivity: responses to UK-14304, B-HT 920 and cirazoline, which had a relatively slow speed of onset of contraction were not affected. There was no correlation between enhancement and alpha-adrenoceptor sub-type although the agonists which were enhanced all activate alpha 1-adrenoceptors. Competitive antagonists failed to reveal an alpha-adrenoceptor subtype enhanced by endothelial disruption. However, effects of phenoxybenzamine suggest that alpha 1-adrenoceptors are necessary for the influence of basal EDRF.
authors.affiliation: Institute of Physiology, University of Glasgow.
authors.forename: J C
authors.initials: JC
authors.lastname: McGrath
authors.forename: S
authors.initials: S
authors.lastname: Monaghan
authors.forename: A G
authors.initials: AG
authors.lastname: Templeton
authors.forename: V G
authors.initials: VG
authors.lastname: Wilson
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology*; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D005260:Female; D005480:Flurbiprofen / Q000494:pharmacology; D006454:Hemoglobins / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D009599:Nitroprusside / Q000494:pharmacology; D011817:Rabbits; D012501:Saphenous Vein / Q000187:drug effects; D014680:Veins / Q000187:drug effects / Q000378:metabolism
chemical_list: D000316:Adrenergic alpha-Agonists; D006454:Hemoglobins; D009599:Nitroprusside; D009569:Nitric Oxide; D005480:Flurbiprofen; D000109:Acetylcholine