Stimulation of perivascular nitric oxide synthesis by oxygen
SR Thom, D Fisher, J Zhang… - American Journal …, 2003 - journals.physiology.org
SR Thom, D Fisher, J Zhang, VM Bhopale, ST Ohnishi, Y Kotake, T Ohnishi, DG Buerk
American Journal of Physiology-Heart and Circulatory Physiology, 2003•journals.physiology.orgWe hypothesized that elevated partial pressures of O2 would increase perivascular nitric
oxide (· NO) synthesis. Rodents with O2-and· NO-specific microelectrodes implanted
adjacent to the abdominal aorta were exposed to O2 at partial pressures from 0.2 to 2.8
atmospheres absolute (ATA). Exposures to 2.0 and 2.8 ATA O2 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 …
oxide (· NO) synthesis. Rodents with O2-and· NO-specific microelectrodes implanted
adjacent to the abdominal aorta were exposed to O2 at partial pressures from 0.2 to 2.8
atmospheres absolute (ATA). Exposures to 2.0 and 2.8 ATA O2 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 …
We hypothesized that elevated partial pressures of O2 would increase perivascular nitric oxide (·NO) synthesis. Rodents with O2- and ·NO-specific microelectrodes implanted adjacent to the abdominal aorta were exposed to O2 at partial pressures from 0.2 to 2.8 atmospheres absolute (ATA). Exposures to 2.0 and 2.8 ATA O2 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 O2appeared to be due to an altered cellular redox state. Exposure to 2.8 ATA O2, but not 2.0 ATA O2, 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 O2. 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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