Redox signaling of the arteriolar myogenic response

Arteriolar vascular smooth muscle cells (VSMCs) are mechanosensitive, const ricting to elevations in transmural pressure (P-TM). The goal of the presen t study was to determine using mouse isolated tail arterioles and arteries whether oxidant signaling regulates this myogenic response. In response to P-TM elevation, VSMCs of arterioles but not arteries generated constriction and increased reactive oxygen species (ROS) activity (using the H2O2-sensi tive probe dichlorodihydrofluorescein). Arterioles had increased expression of NADPH oxidase components compared with arteries. Inhibition of NADPH ox idase, using mice with targeted impairment of enzyme components (p47(phox) or rac1) or diphenyleneiodonium, prevented the pressure-induced generation of ROS. When ROS activity was inhibited, either by inhibiting NADPH oxidase or with N-acetylcysteine, the myogenic constriction was abolished. The myo genic. constriction was also inhibited by catalase, which inactivates H2O2, but was unaffected by a cell-permeant mimic of superoxide dismutase (MnTMP yP). alpha (1)-Adrenergic constriction was not associated with altered ROS activity and was not affected by inhibition of NADPH oxidase or ROS. Exogen ous H2O2 constricted VSMCs of arterioles but not arteries. Thus, NADPH oxid ase and ROS, in particular H2O2 contribute to the myogenic: response of art eriolar VSMCs.