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An endothelium-dependent contraction induced by acetylcholiine in isolated rabbit aorta
1787 P.th.141 I
An endothelium-dependent contraction induced by acetylcholine in isolated rabbit aorta Singh, M. and Mittra, S. Unit of Cardiovascular Pharmacology, Faculty of Pharmaceutical Sciences. Basic Medical Sciences Block, Panjab University, Chandigarh 160014. India
Rabbits of Belgium strain used in this study were ne,.ther hypertensive nor hyperglycaemic. Moreover aortae of these animals did not demonstrate any visible sign of atherosclerosis. Cumulative dose-response curve of acetylcholine in isolated rabbit aorta with intact and denuded endothelium was employed. Effect of superoxide dismutase, catalase and pyrogallol was examined on cumulative dose-response curve (CDRC) of acetylcholine to delineate the possible role of oxygen free radical on endothelium dependent contractions of acetylcholine. Involvement of arachidonic acid metabolites in endothelium dependent contractions of acetylcholine was investigated by studying the effect of OKY-046, a thromboxane synthetase inhibitor and indomethacin, a cyclooxygenase inhibtor on CDRC of acetylcholine. Acetylcholine-evoked contractions in isolated rabbit aorta are endothelium dependent because removal of endothelium attenuated these contractions. Moreover contractions induced by acetylcholine are mediated through muscarinic receptors. But phenylepherine-evoked contractions are not endothelium dependent. Superoxide dismutase potentiated the contractile responses of acetylcholine, perhaps by preventing the inactivation of endothelium derived contracting factor (EDCF) with superoxide anion. Hydrogen peroxide may not be responsible for the inactivation of proposed EDCF because catalase treatment did not alter the contractile responses of acetylcholine. Moreover EDCF released in rsponse to acetylcholine do not appear to be superoxide anion because superoxide anion generator, pyrogallol has attenuated acetylcholine-evoked endothelium dependent contractions. Acetycholine induced contractions are inhibited with indomethacin, a cyclooxygenase inhibitor but they are not affected by OKY-046, a thromboxane synthetase inhibitor. These observations suggest that endothelium-dependent contractions of acetylcholine in isolated rabbit aorta may be mediated through the release of an unknown contracting factor and this contracting factor is not a superoxide anion. It may be a cyclooxygenase product other than thromboxanes. I P.th.142 [
Relaxant component in the response of the guinea-pig mesenteric artery to h i s t ~ : n e mediated by the release of the endothelium derived relaxing factor Kxsti6, S.K., Stepanovi6, R.M. and Krsti6 *, M.K. Dept.of Pharmacology, Faculty of Pharmacy, PO Box 146, 11000 Belgrade and * Dept. of Pharmacology, Faculty of Medicine, PO Box 662, 11000 Belgrade, Yugoslavia
It has been shown that histamine relaxes the isolated dog and rat superior mesenteric arteries through the activation of histamine ,41-receptors on the vascular endothelium with consequent release of prostacyclin and the endothelium derived relaxing factor (EDRF), respectively (Toda, 1984; Krsti~ et al., 1988). However, helical strips of the guinea-pig mesenteric artery are contracterd by histamine (Satoh et al., 1984). In the present experiments, an attempt was made to provide evidence that in the response of the isolated quinea-pig mesenteric artery a relaxant component exists and to establish the mechanism of its development. Paired rings (4 mm long) taken from the mesenteric artery of the guinea-pig (350-460 g) were suspended in organ chambers filled with Krebs-Ringer-bicarbonate solution gassed with 95~ O2-5~ CO2 mixture and kept at 37°C (pH = 7,4). In one ring of each pair the control response to histamine was recorded. In some rings the endothelium was mechanically removed. Each ring was gradually stretched to the optimal point (2 g) on its length-tension curve. Isometric tension was continuously recorded.
An endothelium-dependent contraction induced by acetylcholine in isolated rabbit aorta Singh, M. and Mittra, S. Unit of Cardiovascular Pharmacology, Faculty of Pharmaceutical Sciences. Basic Medical Sciences Block, Panjab University, Chandigarh 160014. India
Rabbits of Belgium strain used in this study were ne,.ther hypertensive nor hyperglycaemic. Moreover aortae of these animals did not demonstrate any visible sign of atherosclerosis. Cumulative dose-response curve of acetylcholine in isolated rabbit aorta with intact and denuded endothelium was employed. Effect of superoxide dismutase, catalase and pyrogallol was examined on cumulative dose-response curve (CDRC) of acetylcholine to delineate the possible role of oxygen free radical on endothelium dependent contractions of acetylcholine. Involvement of arachidonic acid metabolites in endothelium dependent contractions of acetylcholine was investigated by studying the effect of OKY-046, a thromboxane synthetase inhibitor and indomethacin, a cyclooxygenase inhibtor on CDRC of acetylcholine. Acetylcholine-evoked contractions in isolated rabbit aorta are endothelium dependent because removal of endothelium attenuated these contractions. Moreover contractions induced by acetylcholine are mediated through muscarinic receptors. But phenylepherine-evoked contractions are not endothelium dependent. Superoxide dismutase potentiated the contractile responses of acetylcholine, perhaps by preventing the inactivation of endothelium derived contracting factor (EDCF) with superoxide anion. Hydrogen peroxide may not be responsible for the inactivation of proposed EDCF because catalase treatment did not alter the contractile responses of acetylcholine. Moreover EDCF released in rsponse to acetylcholine do not appear to be superoxide anion because superoxide anion generator, pyrogallol has attenuated acetylcholine-evoked endothelium dependent contractions. Acetycholine induced contractions are inhibited with indomethacin, a cyclooxygenase inhibitor but they are not affected by OKY-046, a thromboxane synthetase inhibitor. These observations suggest that endothelium-dependent contractions of acetylcholine in isolated rabbit aorta may be mediated through the release of an unknown contracting factor and this contracting factor is not a superoxide anion. It may be a cyclooxygenase product other than thromboxanes. I P.th.142 [
Relaxant component in the response of the guinea-pig mesenteric artery to h i s t ~ : n e mediated by the release of the endothelium derived relaxing factor Kxsti6, S.K., Stepanovi6, R.M. and Krsti6 *, M.K. Dept.of Pharmacology, Faculty of Pharmacy, PO Box 146, 11000 Belgrade and * Dept. of Pharmacology, Faculty of Medicine, PO Box 662, 11000 Belgrade, Yugoslavia
It has been shown that histamine relaxes the isolated dog and rat superior mesenteric arteries through the activation of histamine ,41-receptors on the vascular endothelium with consequent release of prostacyclin and the endothelium derived relaxing factor (EDRF), respectively (Toda, 1984; Krsti~ et al., 1988). However, helical strips of the guinea-pig mesenteric artery are contracterd by histamine (Satoh et al., 1984). In the present experiments, an attempt was made to provide evidence that in the response of the isolated quinea-pig mesenteric artery a relaxant component exists and to establish the mechanism of its development. Paired rings (4 mm long) taken from the mesenteric artery of the guinea-pig (350-460 g) were suspended in organ chambers filled with Krebs-Ringer-bicarbonate solution gassed with 95~ O2-5~ CO2 mixture and kept at 37°C (pH = 7,4). In one ring of each pair the control response to histamine was recorded. In some rings the endothelium was mechanically removed. Each ring was gradually stretched to the optimal point (2 g) on its length-tension curve. Isometric tension was continuously recorded.