dopamine receptor regulation of reactive oxygen species production, NADPH oxidase, and blood pressure. Activation of D1-like receptors (D 1 and/or D5) induces antioxidant responses; however, the mechanism(s) involved in their antioxidant actions are not known. We hypothesized that stimulation of the D 5 receptor inhibits NADPH oxidase activity, and thus the production of reactive oxygen species (ROS). We investigated this issue in D 5 receptor-deficient (D5Ϫ/Ϫ) and wild-type (D 5ϩ/ϩ) mice.

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... oxidase protein expression (gp91 phox , p47 phox , and Nox 4) and activity in kidney and brain, as well as plasma thiobarbituric acid-reactive substances (TBARS) were higher in D 5Ϫ/Ϫ than in D5ϩ/ϩ mice. Furthermore, apocynin, an NADPH oxidase inhibitor, normalized blood pressure, renal NADPH oxidase activity, and plasma TBARS in D 5Ϫ/Ϫ mice. In HEK-293 cells that heterologously expressed human D 5 receptor, its agonist fenoldopam decreased NADPH oxidase activity, expression of one of its subunits (gp91 phox ), and ROS production. The inhibitory effect of the D 5 receptor activation on NADPH oxidase activity was independent of cAMP/PKA but was partially dependent on phospholipase D2. The ability of D5 receptor stimulation to decrease ROS production may explain, in part, the antihypertensive action of D 5 receptor activation. hypertension DURING THE PAST DECADE, DOPAMINE has been shown as an important regulator of blood pressure, sodium balance, and renal and adrenal function through an independent peripheral dopaminergic system (32).