Effects of Oxyhemoglobin on Vasoconstriction in Response to 5-Hydroxytryptamine in Isolated, Perfused Canine Basilar Arteries

Effects of Oxyhemoglobin on Vasoconstriction in Response to 5-Hydroxytryptamine in Isolated,... AbstractOBJECTIVEOxyhemoglobin (OxyHb) is thought to be a critical trigger in the pathogenesis of cerebral vasospasm after aneurysmal subarachnoid hemorrhage. We investigated whether extraluminally applied OxyHb influenced vascular responses to intraluminally applied vasoactive agents in isolated, perfused, canine basilar arteries.METHODSThe steel cannula insertion method was used to examine vascular responses to intraluminally applied 5-hydroxytryptamine (5-HT) receptor agonists, i.e., 5-HT, 5-carboxamidotryptamine (selective for 5-HT1 receptors), and α-methyl-5-hydroxytryptamine (selective for 5-HT2 receptors), potassium chloride, and acetylcholine, before and after extraluminal treatment with OxyHb.RESULTSExtraluminal application of 2.5 × 10−5 mol/L OxyHb immediately induced a transient elevation of the basal perfusion pressure, which gradually decreased and then stabilized at a level slightly higher than the control level. Each 5-HT agonist induced dose-dependent vasoconstriction. The potencies of the agonists were not very different, but the efficacies varied, i.e., α-methyl-5-hydroxytryptamine > 5-HT > 5-carboxamidotryptamine. Each response was strongly inhibited by ketanserin (a selective 5-HT2 receptor antagonist), indicating that each agonist induces vasoconstriction mediated by 5-HT2 receptors. The vasoconstriction in response to each 5-HT2 receptor agonist was consistently potentiated by treatment with OxyHb (2.5 × 10−5 mol/L). 5-HT receptor agonist-induced constrictions after OxyHb treatment were much more markedly inhibited by ketanserin, compared with those before OxyHb treatment. Acetylcholine-induced constrictions were enhanced by OxyHb, but KCI-induced constrictions were significantly decreased by OxyHb.CONCLUSIONIt is suggested that OxyHb enhancement of constrictions in response to 5-HT receptor agonists may be mediated by increased sensitivity of 5-HT, receptors, in addition to actions in the endothelium, in canine basilar arteries. This potentiated vasoconstrictor mechanism may be partially implicated in cerebral vasospasm after subarachnoid hemorrhage. (Neurosurgery 43:1176-1184, 1998) http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Neurosurgery Oxford University Press

Effects of Oxyhemoglobin on Vasoconstriction in Response to 5-Hydroxytryptamine in Isolated, Perfused Canine Basilar Arteries

Effects of Oxyhemoglobin on Vasoconstriction in Response to 5-Hydroxytryptamine in Isolated, Perfused Canine Basilar Arteries

EXPER IM EN TA L S T U D IE S Effects of Oxyhemoglobin on Vasoconstriction in Response to 5-Hydroxytryptamine in Isolated, Perfused Canine Basilar Arteries Yasser I. Orz, M.D., Tsutomu Tsuji, M.D., Toshiki Aoki, M.D., Yu-Shu Yen, M.D., Shigetoshi Chiba, M.D., Shigeaki Kobayashi, M.D. Departments of Neurosurgery (YIO, TT, TA, Y-SY, SK) and Pharmacology (SC), Shinshu University School of Medicine, Matsumoto, lapan O B JE C T IV E : Oxyhem oglobin (O xyH b) is thought to be a critical trigger in the pathogenesis of cerebral vasospasm after aneurysmal subarachnoid hemorrhage. We investigated whether extraluminally applied O x y H b influenced vascular responses to intraluminally applied vasoactive agents in isolated, perfused, canine basilar arteries. M E T H O D S : The steel cannula insertion method was used to examine vascular responses to intraluminally applied 5-hydroxytryptamine (5-H T) receptor agonists, i.e., 5 -H T , 5-carboxamidotryptamine (selective for 5-HT, recep­ tors), and a-methyl-5-hydroxytryptamine (selective for 5 - H T , receptors), potassium chloride, and acetylcholine, before and after extraluminal treatment with O x y H b . RESULTS: Extraluminal application of 2.5 x 1 0 " ’ mol/L O x y H b immediately induced a transient elevation of the basal perfusion pressure, which gradually decreased and then stabilized at a level slightly higher than the control level. Each 5 -H T agonist induced dose-dependent vasoconstriction. The potencies of the agonists were not very different, but the efficacies varied, i.e., a-m ethyl-5-hydroxytryptam ine > 5 -H T > 5 -carboxamidotryptamine. Each response was strongly inhibited by ketanserin (a selective 5 - H T 2 receptor antagonist), indicating that each agonist induces vasoconstriction mediated by 5 -H T , receptors. The vasoconstriction in response to each 5-HT receptor agonist was consistently potentiated by treatment with O x y H b (2.5 x 10 ' mol/L). 5-HT receptor agonist-induced...
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Publisher
Oxford University Press
Copyright
© Published by Oxford University Press.
ISSN
0148-396X
eISSN
1524-4040
D.O.I.
10.1097/00006123-199811000-00089
Publisher site
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Abstract

AbstractOBJECTIVEOxyhemoglobin (OxyHb) is thought to be a critical trigger in the pathogenesis of cerebral vasospasm after aneurysmal subarachnoid hemorrhage. We investigated whether extraluminally applied OxyHb influenced vascular responses to intraluminally applied vasoactive agents in isolated, perfused, canine basilar arteries.METHODSThe steel cannula insertion method was used to examine vascular responses to intraluminally applied 5-hydroxytryptamine (5-HT) receptor agonists, i.e., 5-HT, 5-carboxamidotryptamine (selective for 5-HT1 receptors), and α-methyl-5-hydroxytryptamine (selective for 5-HT2 receptors), potassium chloride, and acetylcholine, before and after extraluminal treatment with OxyHb.RESULTSExtraluminal application of 2.5 × 10−5 mol/L OxyHb immediately induced a transient elevation of the basal perfusion pressure, which gradually decreased and then stabilized at a level slightly higher than the control level. Each 5-HT agonist induced dose-dependent vasoconstriction. The potencies of the agonists were not very different, but the efficacies varied, i.e., α-methyl-5-hydroxytryptamine > 5-HT > 5-carboxamidotryptamine. Each response was strongly inhibited by ketanserin (a selective 5-HT2 receptor antagonist), indicating that each agonist induces vasoconstriction mediated by 5-HT2 receptors. The vasoconstriction in response to each 5-HT2 receptor agonist was consistently potentiated by treatment with OxyHb (2.5 × 10−5 mol/L). 5-HT receptor agonist-induced constrictions after OxyHb treatment were much more markedly inhibited by ketanserin, compared with those before OxyHb treatment. Acetylcholine-induced constrictions were enhanced by OxyHb, but KCI-induced constrictions were significantly decreased by OxyHb.CONCLUSIONIt is suggested that OxyHb enhancement of constrictions in response to 5-HT receptor agonists may be mediated by increased sensitivity of 5-HT, receptors, in addition to actions in the endothelium, in canine basilar arteries. This potentiated vasoconstrictor mechanism may be partially implicated in cerebral vasospasm after subarachnoid hemorrhage. (Neurosurgery 43:1176-1184, 1998)

Journal

NeurosurgeryOxford University Press

Published: Nov 1, 1998

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