Superoxide modulates myogenic contractions of mouse afferent arterioles

Abstract

Reactive oxygen species are reported to enhance or impair renal autoregulation. Since both superoxide and hydrogen peroxide can be vasoconstrictors, we tested the hypothesis that stretch generates superoxide and/or hydrogen peroxide that mediate the myogenic response. Increasing perfusion pressure of isolated renal afferent arteriole in mouse from 40 to 80 mmHg reduced the diameter by 13.3 ± 1.8 % (p<0.001) and increased reactive oxygen species, indexed by ethidium: dihydroethidium fluorescence, by 7.3 ± 2.1% (p<0.05). Stretch-induced fluorescence was prevented by incubation of vessels with tempol or pegylated superoxide dismutase (SOD) but not with pegylated catalase (CAT), relating it to vascular superoxide. Compared to vehicle, Tempol or SOD both prevented stretch-induced contractions (Tempol: 4.1 ± 1.0 %, p<0.001, and SOD 5.4 ± 0.8 %, p<0.05) whereas contractions persisted with catalase (10.1 ± 1.6 %, NS). Bath addition of tempol had no further effect after SOD but remained fully effective after CAT. Hydrogen peroxide added to vessels with myogenic tone caused constraction only at concentrations of 50 μM (contracted by 8.6 ± 2.9 %) and above. In conclusion, stretch increased afferent arteriolar superoxide which enhanced myogenic contraction of normal mouse perfused renal afferent arterioles.