Angiotensin II (ANG II) produces renal vasoconstriction and increases sodium tubular reabsorption by acting on AT1 receptors and raising intracellular calcium. However, there is evidence indicating that some of the physiological effects of angiotensin II may be partly mediated by increasing NAD(P)H oxidase-derived vascular superoxide (O₂^–) production. Nitric oxide (NO) is an important regulator of renal function. Because the free radical O₂^– reacts with NO, producing peroxynitrite and decreasing its bioavailability, in the present study the role of the interactions between O₂^– and NO in mediating the renal effects of ANG II were evaluated both in vivo and in vitro.

An intrarenal infusion of ANG II (16 and 160 pmol kg^-1 min^-1) reduced renal blood flow (RBF) by -19 and -36 % , glomerular filtration rate (GFR) by -18 and -35%, and also water (UV, by -32 and -11 %) and sodium excretion (U_Na, by -29 and -21 %). ANG II also reduced renal cortical NO activity (measured electrochemically) by -9 and -23 %, and lowered the urinary excretion of nitrites/nitrates (U_NOx) by -12 and -24 %). The AT1 receptor antagonist valsartan (160 nmol kg^-1 min^-1) abolished the renal effects of ANG II. Apocynin (10 µmol kg^-1 min^-1), a NADPH inhibitor, increased renal cortical NO concentration (+38 %) and U_NOx (+56 %), and also reduced the renal vasoconstriction produced by ANG II. Tempol (8 µmol kg^-1 min^-1), a superoxide dismutase mimetic, also raised renal cortical NO activity (+36 %) and U_NOx (+26 %). Pretreatment with apocynin or tempol abolished the effects of ANG II on renal cortical NO concentration, GFR, UV and U_Na. ANG II (10 nM) increased O₂^– generation (measured in vitro as lucigenin chemiluminescence) in renal cortical homogenate by +17 %, while valsartan (10^-5 M), apocynin (6 X 10^-4 M) and tempol (5 X 10^-4 M) reduced basal O₂^– generation by -37, -60 and -30 %, respectively. Also, valsartan, apocynin and tempol abolished the effects of ANG II on O₂^– generation. In addition, ANG II (10^-8 M) raised the generation of peroxynitrite (+21 %) in renal cortical homogenate (measured in vitro as luminol chemiluminescence), and this effect was prevented by valsartan, apocynin and tempol. Overall, these data indicate that the renal vascular and excretory effects of ANG II may be modulated by increased NAD(P)H oxidase-derived O₂^– that reduces renal NO bioavailability.