HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 294/4/F719    most recent 00506.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Just, A. Articles by Arendshorst, W. J. PubMed PubMed Citation Articles by Just, A. Articles by Arendshorst, W. J.

CALL FOR PAPERS
Renal Hemodynamics: Biomolecular Control Mechanisms and Integration of Vascular and Tubular Function

Reactive oxygen species participate in acute renal vasoconstrictor responses induced by ET_A and ET_B receptors

¹Department of Cell and Molecular Physiology, ²Carolina Cardiovascular Biology Center, and ³UNC Kidney Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina

Submitted 27 October 2007 ; accepted in final form 4 February 2008

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-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 O₂^– and may elevate H₂O₂, attenuated ET-1 responses similar to apocynin (by 38 ± 6%, P < 0.01). We conclude that ROS, O₂^– rather than H₂O₂, 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 O₂^– by NO seems to be more important during ET_B stimulation.

renal hemodynamics; vascular smooth muscle; renal vascular resistance; afferent arteriole; oxidative stress; redox signaling; nitric oxide; nitric oxide synthase; superoxide dismutase; endothelin