The effect of subarachnoid hemorrhage on mechanisms of vasodilation mediated by cyclic adenosine monophosphate

Hisashi Onoue, Zvonimir S Katusic

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Object. This study was designed to determine whether subarachnoid hemorrhage (SAH) affects the function of the K+ channels responsible for relaxation of canine cerebral arteries in response to adenylate cyclase activation. Methods. The effect of K+ channel inhibitors on the arterial relaxation response to forskolin, a direct adenylate cyclase activator, was studied in rings of basilar arteries obtained from normal dogs and dogs in which SAH was induced (double-hemorrhage model). The levels of adenosine 3',5'-cyclic monophosphate (cAMP) were measured using the radioimmunoassay technique. In rings with the endothelium removed, relaxation induced by forskolin was not affected by SAH. The relaxation response to forskolin was reduced by charybdotoxin (10-7 mol/L), a selective Ca++-activated K+ channel inhibitor, in normal arteries and arteries subjected to autologous blood injection. This inhibitory effect of charybdotoxin was significantly greater in arteries involved in SAH than in normal vessels. The relaxation response to forskolin was reduced by 4-aminopyridine (10-3 mol/L), a delayed rectifier K+ channel inhibitor, only in arteries involved in SAH. In contrast, the relaxation response to forskolin was not affected by glyburide (10-5 mol/L), an adenosine 5'-triphosphate-sensitive K+ channel inhibitor, in both normal and SAH arteries. Forskolin (3 x 10-7 mol/L) produced an approximately 10-fold increase in levels of cAMP. The basal values and increased levels of cAMP detected after stimulation with forskolin were no different in normal arteries and those exposed to SAH. Conclusions. These results demonstrate that formation of cAMP and the relaxation response to adenylate cyclase activation are not affected by SAH. However, in diseased arteries, K+ channels assume a more important role in the mediation of relaxation response to forskolin, indicating that SAH may change the mechanisms responsible for vasodilation induced by cAMP.

Original languageEnglish (US)
Pages (from-to)111-117
Number of pages7
JournalJournal of Neurosurgery
Volume89
Issue number1
StatePublished - Jul 1998

Fingerprint

Subarachnoid Hemorrhage
Vasodilation
Cyclic AMP
Colforsin
Arteries
Adenylyl Cyclases
Charybdotoxin
Dogs
4-Aminopyridine
Basilar Artery
Cerebral Arteries
Glyburide
Endothelium
Radioimmunoassay
Canidae
Adenosine Triphosphate
Hemorrhage
Injections

Keywords

  • Adenylate cyclase
  • Cerebral vasospasm
  • Cyclic adenosine monophosphate
  • Dog
  • Forskolin
  • Potassium channel inhibitor
  • Subarachnoid hemorrhage

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)

Cite this

The effect of subarachnoid hemorrhage on mechanisms of vasodilation mediated by cyclic adenosine monophosphate. / Onoue, Hisashi; Katusic, Zvonimir S.

In: Journal of Neurosurgery, Vol. 89, No. 1, 07.1998, p. 111-117.

Research output: Contribution to journalArticle

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abstract = "Object. This study was designed to determine whether subarachnoid hemorrhage (SAH) affects the function of the K+ channels responsible for relaxation of canine cerebral arteries in response to adenylate cyclase activation. Methods. The effect of K+ channel inhibitors on the arterial relaxation response to forskolin, a direct adenylate cyclase activator, was studied in rings of basilar arteries obtained from normal dogs and dogs in which SAH was induced (double-hemorrhage model). The levels of adenosine 3',5'-cyclic monophosphate (cAMP) were measured using the radioimmunoassay technique. In rings with the endothelium removed, relaxation induced by forskolin was not affected by SAH. The relaxation response to forskolin was reduced by charybdotoxin (10-7 mol/L), a selective Ca++-activated K+ channel inhibitor, in normal arteries and arteries subjected to autologous blood injection. This inhibitory effect of charybdotoxin was significantly greater in arteries involved in SAH than in normal vessels. The relaxation response to forskolin was reduced by 4-aminopyridine (10-3 mol/L), a delayed rectifier K+ channel inhibitor, only in arteries involved in SAH. In contrast, the relaxation response to forskolin was not affected by glyburide (10-5 mol/L), an adenosine 5'-triphosphate-sensitive K+ channel inhibitor, in both normal and SAH arteries. Forskolin (3 x 10-7 mol/L) produced an approximately 10-fold increase in levels of cAMP. The basal values and increased levels of cAMP detected after stimulation with forskolin were no different in normal arteries and those exposed to SAH. Conclusions. These results demonstrate that formation of cAMP and the relaxation response to adenylate cyclase activation are not affected by SAH. However, in diseased arteries, K+ channels assume a more important role in the mediation of relaxation response to forskolin, indicating that SAH may change the mechanisms responsible for vasodilation induced by cAMP.",
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N2 - Object. This study was designed to determine whether subarachnoid hemorrhage (SAH) affects the function of the K+ channels responsible for relaxation of canine cerebral arteries in response to adenylate cyclase activation. Methods. The effect of K+ channel inhibitors on the arterial relaxation response to forskolin, a direct adenylate cyclase activator, was studied in rings of basilar arteries obtained from normal dogs and dogs in which SAH was induced (double-hemorrhage model). The levels of adenosine 3',5'-cyclic monophosphate (cAMP) were measured using the radioimmunoassay technique. In rings with the endothelium removed, relaxation induced by forskolin was not affected by SAH. The relaxation response to forskolin was reduced by charybdotoxin (10-7 mol/L), a selective Ca++-activated K+ channel inhibitor, in normal arteries and arteries subjected to autologous blood injection. This inhibitory effect of charybdotoxin was significantly greater in arteries involved in SAH than in normal vessels. The relaxation response to forskolin was reduced by 4-aminopyridine (10-3 mol/L), a delayed rectifier K+ channel inhibitor, only in arteries involved in SAH. In contrast, the relaxation response to forskolin was not affected by glyburide (10-5 mol/L), an adenosine 5'-triphosphate-sensitive K+ channel inhibitor, in both normal and SAH arteries. Forskolin (3 x 10-7 mol/L) produced an approximately 10-fold increase in levels of cAMP. The basal values and increased levels of cAMP detected after stimulation with forskolin were no different in normal arteries and those exposed to SAH. Conclusions. These results demonstrate that formation of cAMP and the relaxation response to adenylate cyclase activation are not affected by SAH. However, in diseased arteries, K+ channels assume a more important role in the mediation of relaxation response to forskolin, indicating that SAH may change the mechanisms responsible for vasodilation induced by cAMP.

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