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Updated: Aug 29, 2026
En Face Detection of Nitric Oxide and Superoxide in Endothelial Layer of Intact Arteries
Published on: February 25, 2016
Gene-targeted mice reveal a critical role for inducible nitric oxide synthase in vascular dysfunction during diabetes
Carol A Gunnett1, Donald D Heistad, Frank M Faraci
1Department of Internal Medicine, University of Iowa Carver College of Medicine and Veterans Affairs Medical Center, Iowa City 52242-1081, USA. Carol-Gunnett@uiowa.edu
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.
