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NADPH‐oxidase activity contributes to acute renal vasoconstrictor responses induced by ETA‐ and ETB‐receptors
Author(s) -
Just Armin,
Whitten Christina L.,
Arendshorst William J.
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a498-d
Subject(s) - apocynin , medicine , endocrinology , chemistry , angiotensin ii , kidney , endothelin receptor , nadph oxidase , agonist , superoxide , receptor , renal blood flow , reactive oxygen species , biochemistry , enzyme
Endothelin‐1 (ET‐1) stimulates reactive oxygen species (ROS) in the vasculature and kidney in the chronic setting. Recent results from our lab indicate that superoxide contributes to acute calcium signaling activated by ET‐1 in isolated afferent arterioles. The present study investigated whether ROS contribute to acute renal vasoconstrictor responses of ET A and ET B ‐receptors in the intact kidney in vivo. The responsiveness of renal blood flow (RBF) to acute bolus injection of ET‐1 (3–6 pmol) or ET B ‐agonist sarafotoxin (S6C, 3–6 pmol) into the renal artery (ira) of anesthetized Sprague‐Dawley rats was evaluated in the presence and absence of ET A ‐ (BQ‐123, 7 pmol/min) or ET B ‐receptor antagonism (BQ‐788, 7 pmol/min). Responsiveness to angiotensin II (Ang II, 4 ng) was also tested. ET‐1 reduced RBF by 30±3%, which was attenuated to 15±2% (−45±7%) during inhibition of NAD(P)H‐oxidase by apocynin (4 mg/kg/min ira). Apocynin also diminished the response to S6C from 19±2 to 11±1% (−38%), to ET‐1 during BQ‐123 from 20±6 to 8±1% (−51%), and to ET‐1 during BQ‐788 from 70±10 to 30±2% (−57%). Responses to Ang II were attenuated from 33±5 to 15±2% (−48%). Apocynin alone elevated baseline RBF 9±1% (p<0.05). We conclude that NAD(P)H‐oxidase activity participate in basal vascular tone in the healthy kidney in vivo and contribute ~50% to the acute renal vasoconstrictor effects of both ET A ‐ and ET B ‐receptors as well as to that of Ang II. This indicates general importance of ROS in vasoconstrictor signaling that may extend to other G‐protein coupled receptors. Supported by NIH (HL02334) .