Journal article
Mechanisms that produce nitric oxide-mediated relaxation of cerebral arteries during atherosclerosis
Stroke (1970), Vol.32(3), pp.761-766
2001
DOI: 10.1161/01.STR.32.3.761
PMID: 11239199
Abstract
Background and purpose: The first goal of the present study was to examine the hypothesis that relaxation of cerebral arteries to nitric oxide in primates is dependent on activation of soluble guanylate cyclase (sGC). The second goal was to determine whether the role of sGC in mediating responses to nitric oxide is altered in atherosclerosis.
Methods: Basilar arteries from normal and atherosclerotic monkeys were studied in vitro. After precontraction with prostaglandin F(2alpha) (0.1 to 1 micromol/L), concentration-response curves to authentic nitric oxide (1 nmol/L to 1 micromol/L), sodium nitroprusside (10 nmol/L to 10 micromol/L; a nitric oxide donor), and papaverine (10 nmol/L to 10 micromol/L; a non-nitric oxide, non-sGC-dependent stimulus) were generated in the presence and absence of 1H-[1,2,4]-oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; 1 and 10 micromol/L; an inhibitor of sGC). The effect of ODQ on basal tone of basilar arteries from normal and atherosclerotic monkeys was also examined.
Results: Nitric oxide, sodium nitroprusside, and papaverine produced relaxation that was similar (P:>0.05) in normal and atherosclerotic monkeys. ODQ produced marked inhibition (P:<0.05) of vasorelaxation in response to nitric oxide and nitroprusside but not papaverine. For example, relaxation of the basilar artery in response to nitric oxide (0.1 micromol/L) was inhibited by approximately 85% and 73% by ODQ (1 micromol/L) in normal and atherosclerotic monkeys, respectively. ODQ produced contraction of the basilar arteries, and the increase in tension to ODQ was greater in normal (2.7+/-0.3 g; mean+/-SE) than in atherosclerotic monkeys (1.4+/-0.4 g; P:<0.05). In contrast, contraction to prostaglandin F(2alpha) was similar in the basilar artery from normal and atherosclerotic monkeys.
Conclusions: These findings suggest that (1) relaxation of cerebral arteries in primates in response to nitric oxide is normally dependent, in large part, on activation of sGC and (2) the influence of sGC (via reduced production and/or activity of basal nitric oxide) on cerebral vascular tone is reduced in atherosclerosis.
Details
- Title: Subtitle
- Mechanisms that produce nitric oxide-mediated relaxation of cerebral arteries during atherosclerosis
- Creators
- Sean P DIDION - Departments of Internal Medicine and Pharmacology, Cardiovascular Center, University of Iowa College of Medicine, Iowa City, United StatesDonald D HEISTAD - Departments of Internal Medicine and Pharmacology, Cardiovascular Center, University of Iowa College of Medicine, Iowa City, United StatesFrank M FARACI - Departments of Internal Medicine and Pharmacology, Cardiovascular Center, University of Iowa College of Medicine, Iowa City, United States
- Resource Type
- Journal article
- Publication Details
- Stroke (1970), Vol.32(3), pp.761-766
- Publisher
- Lippincott Williams & Wilkins; Hagerstown, MD
- DOI
- 10.1161/01.STR.32.3.761
- PMID
- 11239199
- ISSN
- 0039-2499
- eISSN
- 1524-4628
- Language
- English
- Date published
- 2001
- Academic Unit
- Cardiovascular Medicine; Neuroscience and Pharmacology; Internal Medicine
- Record Identifier
- 9984040326302771
Metrics
9 Record Views