Document Detail

Effects of methylene blue on hypoxic cerebral vasodilatation in the rabbit.
MedLine Citation:
PMID:  2166799     Owner:  NLM     Status:  MEDLINE    
The present studies were conducted to examine the role of cerebrovascular guanylate cyclase in hypoxic cerebral vasodilatation. In arteries mounted in vitro for measurements of isometric tension, 20 min of hypoxia (bath oxygen partial pressure, approximately 15 Torr) significantly increased cyclic GMP levels from 16 to 32, from 15 to 25 and from 20 to 38 pmol/g in rabbit common carotid, internal carotid and basilar arteries. These increases were blocked either by pretreatment with 3 microM methylene blue, or by removal of the vascular endothelium. Methylene blue also significantly delayed hypoxic relaxation in the basilar and internal carotid arteries, and blocked transient hypoxic vasoconstriction in the common carotid. Together, these in vitro results demonstrate that vascular cytosolic guanylate cyclase participates in an endothelium-dependent manner in the direct effects of hypoxia on cerebral arteries, and that the nature of this participation varies significantly between arteries. When methylene blue (20 mg/kg) was administered in vivo, however, it had no effect on the magnitude of hypoxic cerebral vasodilatation as determined by both local (mass spectrometry) and global (venous outflow) methods of blood flow measurement. This latter finding suggests that: 1) large and small cerebral arteries may differ significantly in terms of either endothelial function or sensitivity to methylene blue; or 2) feedback regulation of other mechanisms of hypoxic cerebral vasodilatation compensate for the effects of guanylate cyclase inhibition. Additional experiments using other inhibitors of cytosolic guanylate cyclase and/or vessels isolated from the cerebral microcirculation will be necessary to distinguish between these possibilities.
W J Pearce; A M Reynier-Rebuffel; J Lee; P Aubineau; L Ignarro; J Seylaz
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of pharmacology and experimental therapeutics     Volume:  254     ISSN:  0022-3565     ISO Abbreviation:  J. Pharmacol. Exp. Ther.     Publication Date:  1990 Aug 
Date Detail:
Created Date:  1990-09-17     Completed Date:  1990-09-17     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0376362     Medline TA:  J Pharmacol Exp Ther     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  616-25     Citation Subset:  IM    
Department of Physiology, Loma Linda University School of Medicine, California.
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MeSH Terms
Anoxia / enzymology*
Cerebrovascular Circulation / drug effects*
Cyclic GMP / metabolism*
Drug Interactions
Injections, Intravenous
Methylene Blue / pharmacology*
Muscle, Smooth, Vascular / drug effects*,  enzymology
Nitroglycerin / pharmacology
Papaverine / pharmacology
Vasodilation / drug effects
Grant Support
Reg. No./Substance:
55-63-0/Nitroglycerin; 58-74-2/Papaverine; 61-73-4/Methylene Blue; 7665-99-8/Cyclic GMP

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