Gene-targeted mice reveal a critical role for inducible nitric oxide synthase in vascular dysfunction during diabetes

Carol A GUNNETT; Donald D HEISTAD; Frank M FARACI

doi:10.1161/01.STR.0000099123.55171.3F

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Gene-targeted mice reveal a critical role for inducible nitric oxide synthase in vascular dysfunction during diabetes

Journal article

Open access

Peer reviewed

Gene-targeted mice reveal a critical role for inducible nitric oxide synthase in vascular dysfunction during diabetes

Carol A GUNNETT, Donald D HEISTAD and Frank M FARACI

Stroke (1970), Vol.34(12), pp.2970-2974

2003

DOI: 10.1161/01.STR.0000099123.55171.3F

PMID: 14657549

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Abstract

Background and purpose: Inducible nitric oxide synthase (iNOS) is a mediator of vascular dysfunction during inflammation. The purpose of this study was to test the hypothesis that vascular dysfunction during diabetes is dependent on expression of iNOS. Methods: Diabetes was produced in mice with streptozotocin (150 mg/kg IP). After 4 to 6 months of diabetes, vasomotor function was examined in vitro in carotid arteries from mice with targeted disruption of the gene for iNOS (iNOS-deficient mice) and from normal, wild-type (WT) mice. Results: Contractile responses of carotid arteries to U46619, a thromboxane A2 analogue, were not altered by diabetes in WT mice. Responses to U46619 were increased in arteries from diabetic iNOS-deficient mice compared with diabetic WT and nondiabetic mice (iNOS-deficient and WT mice). These results indicate that expression of iNOS inhibits an increased vasoconstrictor response during diabetes. Arteries from nondiabetic WT mice relaxed 83+/-2% (mean+/-SE) in response to acetylcholine (1 micromol/L) compared with 58+/-6% in arteries from diabetic WT mice (P<0.05 versus nondiabetic mice). In contrast, relaxation of carotid arteries to acetylcholine was similar (81+/-4% versus 76+/-6%; P>0.05) in iNOS-deficient mice under nondiabetic and diabetic conditions, respectively. Thus, diabetes produced impairment of endothelium-dependent relaxation in arteries from WT but not iNOS-deficient mice. Endothelium-independent relaxation in response to nitroprusside was similar in arteries from all mice. Conclusions: These results provide the first direct evidence that impairment of endothelium-dependent relaxation during diabetes is dependent on expression of iNOS.

Biological and medical sciences

Endocrinopathies

Diabetes. Impaired glucose tolerance

Medical sciences

Endocrine pancreas. Apud cells (diseases)

Associated diseases and complications

Details

Title: Subtitle: Gene-targeted mice reveal a critical role for inducible nitric oxide synthase in vascular dysfunction during diabetes
Creators: Carol A GUNNETT - Department of Internal Medicine, University of Iowa Carver College of Medicine and Veterans Affairs Medical Center, Iowa City, United States
Donald D HEISTAD - Department of Internal Medicine, University of Iowa Carver College of Medicine and Veterans Affairs Medical Center, Iowa City, United States
Frank M FARACI - Department of Internal Medicine, University of Iowa Carver College of Medicine and Veterans Affairs Medical Center, Iowa City, United States
Resource Type: Journal article
Publication Details: Stroke (1970), Vol.34(12), pp.2970-2974
Publisher: Lippincott Williams & Wilkins; Hagerstown, MD
DOI: 10.1161/01.STR.0000099123.55171.3F
PMID: 14657549
ISSN: 0039-2499
eISSN: 1524-4628
Language: English
Date published: 2003
Academic Unit: Cardiovascular Medicine; Neuroscience and Pharmacology; Internal Medicine
Record Identifier: 9984040539302771

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