The Role of Reactive Oxygen Species in Renal Blood Flow Autoregulation

Abstract

Autoregulation of renal blood flow (RBF) is mediated by a myogenic response (MR), tubuloglomerular feedback (TGF) and by a third mechanism that is slower than MR and TGF. Reactive oxygen species (ROS) are known to contribute to acute agonist‐induced renal vasoconstriction and to enhance TGF. Little is known about the role of ROS in RBF autoregulation and underlying mechanisms.Autoregulatory mechanisms were assessed from the response of RBF to a rapid step‐increase in renal artery pressure in rats. MR was derived from resistance changes within the first 5 s, TGF from those between 5 and 25 s, and the third mechanism from 25–100 s. During control, overall autoregulation was 85±6% of perfect. MR provided autoregulatory efficiency of 63±6%, TGF 41±5% and the 3rd mechanism 5±6%. Inhibition of NAD(P)H oxidase by apocynin attenuated overall autoregulation to 62±7% (p<0.05) and MR to 39±4% (p<0.001) but barely affected TGF and 3rd mechanism (32±3 and 14±4%, p>0.06). Inhibition of nitric oxide synthase by LNAME markedly augmented MR (130±16%, p<0.001) leaving little room for TGF and 3rd mechanism. During LNAME, apocynin strongly blunted MR (to 56±11%, p<0.01), reversing the effect of LNAME. The superoxide dismutase (SOD) mimetic tempol tended to diminish MR similar to apocynin (38 vs. 52%, p>0.08).We conclude that ROS contribute to RBF autoregulation by strengthening MR in the normal kidney. This effect is mainly due to superoxide rather than H2O2 and does not require NO but instead is blunted by NO. Superoxide plays a major role in facilitating the modulation of MR by NO in the renal microcirculation.Supported by NIH (HL‐02334) and Arthur C Guyton Award.