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Myogenic contraction is the principal component of renal autoregulation that protects the kidney from hypertensive barotrauma. Contractions are initiated by a rise in perfusion pressure that signals a reduction in membrane potential ( E m ) of vascular smooth muscle cells to activate voltage-operated Ca 2+  channels. Since ROS have variable effects on myogenic tone, we investigated the hypothesis that superoxide (O 2  ·− ) and H 2 O 2  differentially impact myogenic contractions. The myogenic contractions of mouse isolated and perfused single afferent arterioles were assessed from changes in luminal diameter with increasing perfusion pressure (40–80 mmHg). O 2  ·− , H 2 O 2 , and E m  were assessed by fluorescence microscopy during incubation with paraquat to increase O 2  ·−  or with H 2 O 2 . Paraquat enhanced O 2  ·−  generation and myogenic contractions (−42 ± 4% vs. −19 ± 4%, P &lt; 0.005) that were blocked by SOD but not by catalase and signaled via PKC. In contrast, H 2 O 2  inhibited the effects of paraquat and reduced myogenic contractions (−10 ± 1% vs. −19 ± 2%, P &lt; 0.005) and signaled via PKG. O 2  ·−  activated Ca 2+ -activated Cl −  channels that reduced E m , whereas H 2 O 2  activated Ca 2+ -activated and voltage-gated K +  channels that increased E m . Blockade of voltage-operated Ca 2+  channels prevented the enhanced myogenic contractions with paraquat without preventing the reduction in E m . Myogenic contractions were independent of the endothelium and largely independent of nitric oxide. We conclude that O 2  ·−  and H 2 O 2  activate different signaling pathways in vascular smooth muscle cells linked to discreet membrane channels with opposite effects on E m  and voltage-operated Ca 2+  channels and therefore have opposite effects on myogenic contractions.

american journal of physiology. renal physiology./american journal of physiology. renal physiology

Differential effects of superoxide and hydrogen peroxide on myogenic signaling, membrane potential, and contractions of mouse renal afferent arterioles