Abstract
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 (Em) 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 (O2 (·-)) and H2O2 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). O2 (·-), H2O2, and Em were assessed by fluorescence microscopy during incubation with paraquat to increase O2 (·-) or with H2O2 Paraquat enhanced O2 (·-) generation and myogenic contractions (-42 ± 4% vs. -19 ± 4%, P < 0.005) that were blocked by SOD but not by catalase and signaled via PKC. In contrast, H2O2 inhibited the effects of paraquat and reduced myogenic contractions (-10 ± 1% vs. -19 ± 2%, P < 0.005) and signaled via PKG. O2 (·-) activated Ca(2+)-activated Cl(-) channels that reduced Em, whereas H2O2 activated Ca(2+)-activated and voltage-gated K(+) channels that increased Em Blockade of voltage-operated Ca(2+) channels prevented the enhanced myogenic contractions with paraquat without preventing the reduction in Em Myogenic contractions were independent of the endothelium and largely independent of nitric oxide. We conclude that O2 (·-) and H2O2 activate different signaling pathways in vascular smooth muscle cells linked to discreet membrane channels with opposite effects on Em and voltage-operated Ca(2+) channels and therefore have opposite effects on myogenic contractions.