1 research outputs found
Effects of hydrogen peroxide on relaxation through the NO/sGC/cGMP pathway in isolated rat iliac arteries
<div><p></p><p>The production of reactive oxygen species, including hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>), is increased in diseased blood vessels. Although H<sub>2</sub>O<sub>2</sub> leads to impairment of the nitric oxide (NO)/soluble guanylate cyclase (sGC)/cGMP signaling pathway, it is not clear whether this reactive molecule affects the redox state of sGC, a key determinant of NO bioavailability. To clarify this issue, mechanical responses of endothelium-denuded rat external iliac arteries to BAY 41-2272 (sGC stimulator), BAY 60-2770 (sGC activator), nitroglycerin (NO donor), acidified NaNO<sub>2</sub> (exogenous NO) and 8-Br-cGMP (cGMP analog) were studied under exposure to H<sub>2</sub>O<sub>2</sub>. The relaxant response to BAY 41-2272 (<i>pD</i><sub>2</sub>: 6.79βΒ±β0.10 and 6.62βΒ±β0.17), BAY 60-2770 (<i>pD</i><sub>2</sub>: 9.57βΒ±β0.06 and 9.34βΒ±β0.15) or 8-Br-cGMP (<i>pD</i><sub>2</sub>: 5.19βΒ±β0.06 and 5.24βΒ±β0.08) was not apparently affected by exposure to H<sub>2</sub>O<sub>2</sub>. In addition, vascular cGMP production stimulated with BAY 41-2272 or BAY 60-2770 in the presence of H<sub>2</sub>O<sub>2</sub> was identical to that in its absence. On the other hand, nitroglycerin-induced relaxation was markedly attenuated by exposing the arteries to H<sub>2</sub>O<sub>2</sub> (<i>pD</i><sub>2</sub>: 8.73βΒ±β0.05 and 8.30βΒ±β0.05), which was normalized in the presence of catalase (<i>pD</i><sub>2</sub>: 8.59βΒ±β0.05). Likewise, H<sub>2</sub>O<sub>2</sub> exposure impaired the relaxant response to acidified NaNO<sub>2</sub> (<i>pD</i><sub>2</sub>: 6.52βΒ±β0.17 and 6.09βΒ±β0.16). These findings suggest that H<sub>2</sub>O<sub>2</sub> interferes with the NO-mediated action, but the sGC redox equilibrium and the downstream target(s) of cGMP are unlikely to be affected in the vasculature.</p></div