Superoxide production mediates acute vasoconstrictor responses to angiotensin II in the kidney by a mechanism largely independent of scavenging of nitric oxide

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Superoxide anion (O2−) and other reactive oxygen species (ROS) are involved in vasoconstriction of angiotensin (Ang II)-induced hypertension. The effects are thought to be mediated largely via O2− scavenging of the vasodilator nitric oxide (NO). Little is known about the role of ROS in acute responses to Ang II in normotensive animals. We investigated the responsiveness of renal blood flow (RBF) to bolus injection of Ang II (4 ng) into the renal artery (ira) of anesthetized Sprague-Dawley rats. During control, this reduced RBF by 24 ± 4 %. Infusion of the superoxide dismutase (SOD) mimetic tempol (1.5–5 mg/kg/min ira) dose-dependently reduced this responsiveness to Ang II by up to 48 ± 6 % (p<0.001). The same was observed during inhibition of O2− production by apocynin (1–4 mg/kg/min ira) with maximum inhibition of 44 ± 5 % (p<0.01). During NO-synthase (NOS)-inhibition (L-NAME, 25 mg/kg iv), tempol reduced reactivity to Ang II by 58 ± 5 %. Similarly, the NAD(P)H-oxidase inhibitor apocynin reduced renal vasoconstriction induced by Ang II during L-NAME by 35 ± 14 %. We conclude that O2− substantially contributes to signaling of acute renal vasoconstrictor responses to Ang II. This effect is largely independent of the presence of NO. Supported by the NIH (HL02334).