Reactive oxygen species participate in acute renal vasoconstrictor responses induced by ET A and ET B receptors

Reactive oxygen species (ROS) play important roles in renal vasoconstrictor responses to acute and chronic stimulation by angiotensin II and norepinephrine, as well as in long-term effects of endothelin-1 (ET-1). Little is known about participation of ROS in acute vasoconstriction produced by ET-1. We tested the influence of NAD(P)H oxidase inhibition by apocynin [4 mg·kg −1 ·min −1 , infused into the renal artery (ira)] on ET A and ET B receptor signaling in the renal microcirculation. Both receptors were stimulated by ET-1, ET A receptors by ET-1 during ET B antagonist BQ-788, and ET B by ET B agonist sarafotoxin 6C. ET-1 (1.5 pmol injected ira) reduced renal blood flow (RBF) 17 ± 4%. Apocynin raised baseline RBF (+10 ± 1%, P < 0.001) and attenuated the ET-1 response to 10 ± 2%, i.e., 35 ± 9% inhibition ( P < 0.05). Apocynin reduced ET A -induced vasoconstriction by 42 ± 12% ( P < 0.05) and that of ET B stimulation by 50 ± 8% ( P < 0.001). During nitric oxide (NO) synthase inhibition ( N ω -nitro-l-arginine methyl ester), apocynin blunted ET A -mediated vasoconstriction by 60 ± 8% ( P < 0.01), whereas its effect on the ET B response (by 87 ± 8%, P < 0.001) was even larger without than with NO present ( P < 0.05). The cell-permeable superoxide dismutase mimetic tempol (5 mg·kg −1 ·min −1 ira), which reduces O 2 − and may elevate H 2 O 2 , attenuated ET-1 responses similar to apocynin (by 38 ± 6%, P < 0.01). We conclude that ROS, O 2 − rather than H 2 O 2 , contribute substantially to acute renal vasoconstriction elicited by both ET A and ET B receptors and to basal renal vasomotor tone in vivo. This physiological constrictor action of ROS does not depend on scavenging of NO. In contrast, scavenging of O 2 − by NO seems to be more important during ET B stimulation.