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Stimulation of perivascular nitric oxide synthesis by oxygen
Journal article   Peer reviewed

Stimulation of perivascular nitric oxide synthesis by oxygen

Stephen R. Thom, Donald Fisher, Jie Zhang, Veena M. Bhopale, S. Tsuyoshi Ohnishi, Yashige Kotake, Tomoko Ohnishi and Donald G. Buerk
American journal of physiology. Heart and circulatory physiology, v 284(4), pp H1230-H1239
01 Apr 2003
PMID: 12505879

Abstract

We hypothesized that elevated partial pressures of O 2 would increase perivascular nitric oxide (·NO) synthesis. Rodents with O 2 - and ·NO-specific microelectrodes implanted adjacent to the abdominal aorta were exposed to O 2 at partial pressures from 0.2 to 2.8 atmospheres absolute (ATA). Exposures to 2.0 and 2.8 ATA O 2 stimulated neuronal (type I) NO synthase (nNOS) and significantly increased steady-state ·NO concentration, but the mechanism for enzyme activation differed at each partial pressure. At both pressures, elevations in ·NO concentration were inhibited by the nNOS inhibitor 7-nitroindazole and the calcium channel blocker nimodipine. Enzyme activation at 2.0 ATA O 2 appeared to be due to an altered cellular redox state. Exposure to 2.8 ATA O 2 , but not 2.0 ATA O 2 , increased nNOS activity by enhancing nNOS association with calmodulin, and an inhibitory effect of geldanamycin indicated that the association was facilitated by heat shock protein 90. Infusion of superoxide dismutase inhibited ·NO elevation at 2.8 but not 2.0 ATA O 2 . Hyperoxia increased the concentration of ·NO associated with hemoglobin. These findings highlight the complexity of oxidative stress responses and may help explain some of the dose responses associated with therapeutic applications of hyperbaric oxygen.

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Collaboration types
Domestic collaboration
Web of Science research areas
Cardiac & Cardiovascular Systems
Peripheral Vascular Disease
Physiology
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