Reactive oxygen species attenuate vasoconstrictor responses in mice overexpressing p22 phox

The role of H 2 O 2 in modulating arterial tone is complex and somewhat ambiguous, as previous studies report roles for H 2 O 2 in both vasoconstriction and relaxation. In this study, isometric tension recording was utilized to measure force generation in response to cumulative concentrations of prostaglandin F2α and phenylephrine in denuded aortic rings obtained from male Tg p22smc mice (bred to overexpress the p22 phox subunit of the NAD(P)H oxidase selectively in VSMC) and negative controls (WT). We tested the hypothesis that overexpression of p22 phox , which increases VSMC H 2 O 2 production, would lead to altered vasoconstrictor responses. In the absence of any change in vascular sensitivity, overexpression of p22 phox resulted in decreased contractile force generation in response to both agonists. Pretreatment with PEG‐catalase normalized contractile responses in rings from Tg p22smc mice implicating ROS as a mediator of the attenuated vasoconstrictor responses. Ca 2+ ‐sensitization via Rho‐kinase activity, K + and Ca 2+ channel function in rings from Tg p22smc mice were unaffected by the increased ROS. Conversely, PKC inhibition attenuated constrictor responses significantly more in rings from WT than Tg p22smc mice, suggesting that chronically elevated vascular H 2 O 2 may reduce PKC activity that results in decreased agonist‐mediated force generation in the vasculature of Tg p22smc mice. (AHA‐SDG 03300119N)