Journal article
Effects of a Novel Inhibitor of Guanylyl Cyclase on Dilator Responses of Mouse Cerebral Arterioles
Stroke (1970), Vol.28(4), pp.837-843
04/1997
DOI: 10.1161/01.STR.28.4.837
PMID: 9099205
Abstract
Background and purpose: Nitric oxide-induced vasodilatation is mediated by both cGMP-dependent and -independent mechanisms. Previous studies that examined the role of soluble guanylyl cyclase in cerebral vessels have used methylene blue and LY-83583, compounds that generate superoxide anion and are not specific for inhibition of soluble guanylyl cyclase. We examined the effects of ODQ (1H-[1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one), a novel and highly selective inhibitor of soluble guanylyl cyclase, on responses of cerebral arterioles.
Methods: The effects of ODQ on responses of cerebral arterioles to acetylcholine, nitroprusside, 8-bromo-cGMP, and adenosine were examined in anesthetized mice by means of a cranial window. The effects of two concentrations of ODQ were examined in the absence and presence of superoxide dismutase. The effects of NG-nitro-L-arginine, an inhibitor of nitric oxide synthase, were also tested.
Results: ODQ (3 and 10 mumol/L) produced concentration-dependent inhibition of dilatation of cerebral arterioles (control diameter = 29 +/- 1 microns) (mean +/- SE) in response to acetylcholine and nitroprusside. For example, 10 mumol/L acetylcholine and 1 mumol/L nitroprusside dilated cerebral arterioles by 28 +/- 3% and 44 +/- 2% in the absence and 6 +/- 2% and 7 +/- 1%, respectively, in the presence of 10 mumol/L ODQ (P < .05 versus control). The inhibitory effects of ODQ were not altered by superoxide dismutase. Vasodilatation in response to 8-bromo-cGMP and adenosine was not inhibited by ODQ. NG-Nitro-L-arginine (100 mumol/L), an inhibitor of nitric oxide synthase, inhibited responses to acetylcholine by approximately 80% but tended to enhance responses to nitroprusside.
Conclusions: Thus, nitric oxide-mediated dilatation of mouse cerebral arterioles is profoundly inhibited by ODQ, an inhibitor of activity of soluble guanylyl cyclase. Cerebral vasodilator responses to adenosine and 8-bromo-cGMP were preserved in the presence of ODQ, indicating that inhibition by ODQ was selective. In contrast to previously used inhibitors of soluble guanylyl cyclase (methylene blue and LY-83583), the effects of ODQ are not mediated by generation of superoxide anion.
Details
- Title: Subtitle
- Effects of a Novel Inhibitor of Guanylyl Cyclase on Dilator Responses of Mouse Cerebral Arterioles
- Creators
- Christopher G Sobey - From the Departments of Internal Medicine and Pharmacology, Cardiovascular Center, University of Iowa College of Medicine, Iowa CityFrank M Faraci - From the Departments of Internal Medicine and Pharmacology, Cardiovascular Center, University of Iowa College of Medicine, Iowa City
- Resource Type
- Journal article
- Publication Details
- Stroke (1970), Vol.28(4), pp.837-843
- DOI
- 10.1161/01.STR.28.4.837
- PMID
- 9099205
- ISSN
- 0039-2499
- eISSN
- 1524-4628
- Comment
- Has Comment: Effects of a Novel Inhibitor of Guanylyl Cyclase on Dilator Responses of Mouse Cerebral Arterioles. Stroke A Journal of Cerebral Circulation, 28 (7), 1467-1468.
- Language
- English
- Date published
- 04/1997
- Academic Unit
- Cardiovascular Medicine; Neuroscience and Pharmacology; Internal Medicine
- Record Identifier
- 9984040491802771
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