Journal article
Gene transfer of inducible nitric oxide synthase impairs relaxation in human and rabbit cerebral arteries
Stroke (1970), Vol.33(9), pp.2292-2296
09/2002
DOI: 10.1161/01.STR.0000027427.86177.D4
PMID: 12215601
Abstract
These studies evaluated whether gene transfer of inducible nitric oxide synthase (iNOS) is a sufficient stimulus to produce vascular dysfunction in cerebral arteries. Methods— Intracranial (pial) arteries were dissected from human brain tissue obtained during elective surgery. Isolated human arteries were incubated in vitro with adenovirus containing iNOS (AdiNOS) or a nonexpressive transgene (control, AdBglII) (500 μL, 3×109 plaque-forming units per milliliter), and vascular function was examined 24 hours later. In anesthetized rabbits, AdiNOS or AdBglII (300 μL 1×1010) was injected into the cisterna magna. Three days later, the basilar artery was removed, and reactivity was examined ex vivo.
Results— In submaximally precontracted vessels, we observed impairment of NO-dependent relaxation in human cerebral arteries after gene transfer of iNOS. Maximum relaxation to bradykinin (1 μmol/L, an endothelium-dependent agonist) was 77±11% (mean±SE) after AdBglII and 31±22% (P<0.05) after AdiNOS. After AdiNOS, responses to nitroprusside (an endothelium-independent NO donor) also were impaired. Responses to both nitroprusside and bradykinin were improved by aminoguanidine (300 μmol/L), an inhibitor of iNOS. AdiNOS produced no change in vasoconstrictor responses to U46619. In basilar arteries from rabbits examined in vitro after gene transfer in vivo, responses to histamine, serotonin, and nitroprusside all were similar after AdiNOS or AdBglII. In contrast, relaxation to acetylcholine was significantly depressed after AdiNOS. Maximum relaxation to acetylcholine (10 μmol/L) was 90±3% after AdBglII and 68±5% (P<0.05) after AdiNOS. Relaxation of arteries after AdiNOS was improved by aminoguanidine.
Conclusions— These studies suggest that expression of iNOS may impair NO-dependent relaxation in both human and rabbit cerebral arteries.
Details
- Title: Subtitle
- Gene transfer of inducible nitric oxide synthase impairs relaxation in human and rabbit cerebral arteries
- Creators
- C A Gunnett - Department of Medicine, University of Iowa College of Medicine and Veterans Affairs Medical Center, Iowa City, Iowa 52242-1081, USA. Carol-Gunnett@uiowa.eduD D LundM A Howard IIIY ChuF M FaraciD D Heistad
- Resource Type
- Journal article
- Publication Details
- Stroke (1970), Vol.33(9), pp.2292-2296
- Publisher
- United States
- DOI
- 10.1161/01.STR.0000027427.86177.D4
- PMID
- 12215601
- ISSN
- 0039-2499
- eISSN
- 1524-4628
- Grant note
- HL62984 / NHLBI NIH HHS NS24621 / NINDS NIH HHS HL14388 / NHLBI NIH HHS HL38901 / NHLBI NIH HHS HL16066 / NHLBI NIH HHS DK54759 / NIDDK NIH HHS
- Language
- English
- Date published
- 09/2002
- Academic Unit
- Neurology; Iowa Neuroscience Institute; Cardiovascular Medicine; Neuroscience and Pharmacology; Neurosurgery; Otolaryngology; Internal Medicine
- Record Identifier
- 9984020988402771
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