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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2001;21:1259.)
© 2001 American Heart Association, Inc.

Editorials

Inducible NO Synthesis in the Vasculature

Molecular Context Defines Physiological Response

Joseph Loscalzo

From the Whitaker Cardiovascular Institute and Evans Department of Medicine, Boston University School of Medicine, Boston, Mass.

Correspondence to Dr Joseph Loscalzo, Whitaker Cardiovascular Institute and Evans Department of Medicine, Boston University School of Medicine, 80 East Concord, W507, Boston, MA 02118. E-mail jloscalz@bu.edu

Key Words: Editorials • endothelial NO synthase • inducible NO synthase • vasculature

Nitric oxide synthesized by endothelial NO synthase (eNOS) is a principal mediator of smooth muscle relaxation in the normal blood vessel. With inflammation, however, inducible NO synthase (iNOS) is expressed in the vessel wall, including the adventitia,¹ and is associated with impaired endothelium-dependent vasorelaxation² and impaired vasoconstriction.^3,4 The molecular mechanism(s) underlying these alterations in vasomotor function accompanying inflammation remains unknown, although in vitro studies suggest that proinflammatory stimuli reduce the expression of eNOS, agonist-mediated cytosolic calcium mobilization, and NO production.⁵

See page 1281

In this issue of Arteriosclerosis, Thrombosis, and Vascular Biology, Gunnett et al⁶ attempt to address the basis for impaired vasomotor responses in inflammation by transferring the iNOS gene to blood vessels. They argue that all prior studies suffer from the lack of selectivity of the pharmacological inhibitors of iNOS used and from the concomitant changes in the expression of other vascular gene products accompanying the inflammatory response and, thus, do not permit an unequivocal assessment of the role of iNOS in these vasomotor abnormalities. They used an adenoviral vector construct containing the mouse iNOS gene to transfer the gene to rabbit carotid arteries in vitro and in vivo. They observed that iNOS gene transfer in vitro led to impaired contractile responses and impaired relaxation responses to endothelium-dependent (acetylcholine and ADP) and endothelium-independent (A23187) agonists, as well as to a direct nitrovasodilator (sodium nitroprusside); NO-independent responses to 8-bromo-cGMP and papaverine were normal. In vivo, they observed that iNOS gene transfer had no effect on contractile responses but . . . [Full Text of this Article]

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