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Factors inducing endothelium‐dependent relaxation in the guinea‐pig basilar artery as estimated from the actions of haemoglobin
Author(s) -
Nishiye E.,
Nakao K.,
Itoh T.,
Kuriyama H.
Publication year - 1989
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.1476-5381.1989.tb11864.x
Subject(s) - contraction (grammar) , acetylcholine , basilar artery , isometric exercise , hyperpolarization (physics) , chemistry , medicine , muscle contraction , endocrinology , endothelium , electrophysiology , anatomy , endoplasmic reticulum , cyclopiazonic acid , vasodilation , depolarization , biophysics , biology , biochemistry , stereochemistry , nuclear magnetic resonance spectroscopy
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 A 2 (STA 2 ) and by high K + were enhanced by haemoglobin (oxyhaemoglobin, Hb) in a concentration‐dependent fashion (above 1 μ m ). 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 STA 2 and by high K + were greater in endothelium‐denuded tissues, but Hb (below 10 μ m ) had no effect on them. 3 Hb (10 μ m ) had no effect on the contractile proteins as estimated from the actions of Hb on Ca 2+ ‐induced contractions in skinned muscle tissues. Further, Hb had no effect on the release of Ca 2+ from intracellular stores but it accelerated the Ca 2+ accumulation into the sarcoplasmic reticulum as judged from the caffeine‐ or STA 2 ‐induced contraction generated in intact tissues. 4 Acetylcholine (ACh) relaxed tissues that were precontracted by STA 2 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 STA 2 (up to 100 n m ) did not modify the resting membrane potential of smooth muscle cells of the basilar artery. ACh (10 μ m ) caused transient hyperpolarization which was only slightly inhibited by Hb (10 μ m ) whether or not STA 2 was present. The hyperpolarization induced by ACh required the presence of endothelial cells. 6 A23187 (0.01–1 μ m ) relaxed tissues which were precontracted by STA 2 , 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 STA 2 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.