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  • Title: Reactive oxygen species participate in acute renal vasoconstrictor responses induced by ETA and ETB receptors.
    Author: Just A, Whitten CL, Arendshorst WJ.
    Journal: Am J Physiol Renal Physiol; 2008 Apr; 294(4):F719-28. PubMed ID: 18256310.
    Abstract:
    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(omega)-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.
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