title: Factors inducing endothelium-dependent relaxation in the guinea-pig basilar artery as estimated from the actions of haemoglobin.
abstract: 1. Factors inducing dilatation of guinea-pig basilar artery were investigated in intact and endothelium-denuded tissues by measurement of isometric tension and by electrophysiological methods. 2. The amplitudes of contractions induced by 9,11,epithio-11,12-methanothromboxane A2 (STA2) and by high K+ were enhanced by haemoglobin (oxyhaemoglobin, Hb) in a concentration-dependent fashion (above 1 microM). For the high K+-induced contraction, the initial tonic component was enhanced to a greater extent than the secondary phasic component. Mechanical responses evoked by STA2 and by high K+ were greater in endothelium-denuded tissues, but Hb (below 10 microM) had no effect on them. 3. Hb (10 microM) had no effect on the contractile proteins as estimated from the actions of Hb on Ca2+-induced contractions in skinned muscle tissues. Further, Hb had no effect on the release of Ca2+ from intracellular stores but it accelerated the Ca2+ accumulation into the sarcoplasmic reticulum as judged from the caffeine- or STA2-induced contraction generated in intact tissues. 4. Acetylcholine (ACh) relaxed tissues that were precontracted by STA2 but Hb prevented this relaxation, in a concentration-dependent fashion. The ACh-induced relaxation was sustained for over 10 min in the absence of Hb, but following application of Hb, ACh caused only a transient relaxation. 5. STA2 (up to 100 nM) did not modify the resting membrane potential of smooth muscle cells of the basilar artery. ACh (10 microM) caused transient hyperpolarization which was only slightly inhibited by Hb (10 microM) whether or not STA2 was present. The hyperpolarization induced by ACh required the presence of endothelial cells. 6. A23187 (0.01-1 microM) relaxed tissues which were precontracted by STA2, in a concentration-dependent fashion but had no effect on the membrane potential. 7. These results suggest that in guinea-pig basilar artery, ACh induces relaxation of tissues that were precontracted by STA2 by causing release of both endothelium-derived relaxing (EDRF) and endothelial dependent hyperpolarizing factor (EDHF) (sustained and initial transient relaxation, respectively), but via different mechanisms. Hb inhibits the former and to a lesser extent, the latter. Since A23187 produced relaxation of pre-contracted tissue but caused no detectable change in the membrane potential, this agent may release EDRF but not EDHF.
authors: Department of Pharmacology, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
authors: E
authors: E
authors: Nishiye
authors: K
authors: K
authors: Nakao
authors: T
authors: T
authors: Itoh
authors: H
authors: H
authors: Kuriyama
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001488:Basilar Artery / Q000187:drug effects / Q000502:physiology; D001685:Biological Factors / Q000494:pharmacology; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D005260:Female; D006168:Guinea Pigs; D006454:Hemoglobins / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D008566:Membranes / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009569:Nitric Oxide; D010108:Oxyhemoglobins / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D001685:Biological Factors; D006454:Hemoglobins; D010108:Oxyhemoglobins; D009569:Nitric Oxide; D002110:Caffeine; D013928:Thromboxane A2; C037866:STA 2; D000109:Acetylcholine; D011188:Potassium; D002118:Calcium