Superoxide scavenging attenuates renal responses to ANG II during nitric oxide synthase inhibition in anesthetized dogs

Abstract

To assess the role of superoxide (O2-) and nitric oxide (NO) interaction in mediating the renal actions of ANG II, we examined the renal responses to intra-arterial infusion of ANG II (0.5 ng x kg(-1) x min(-1)) before and during administration of a superoxide dismutase mimetic, tempol (0.5 mg x kg(-1) x min(-1)), in the presence or absence of NO synthase inhibitor, nitro-L-arginine (NLA; 50 microg x kg(-1) x min(-1)), in anesthetized dogs pretreated with enalaprilat (33 microg x kg(-1) x min(-1)). In one group of dogs (n = 7), ANG II infusion before tempol infusion caused decreases of 24 +/- 4% in renal blood flow (RBF), 55 +/- 7% in urine flow (V), and 53 +/- 8% in urinary sodium excretion (U(Na)V) with a slight decrease in glomerular filtration rate (GFR; -7.8 +/- 3.4%). Tempol infusion alone did not cause significant alterations in RBF, GFR, V, or U(Na)V; however, ANG II in the presence of tempol caused a smaller degree of decreases in RBF (-12 +/- 2%), in V (-16 +/- 5%), and in U(Na)V (-27 +/- 10%) with a slight increase in GFR (6.6 +/- 2.8%) than the responses observed before tempol. In another group of NLA-treated dogs (n = 6), tempol infusion also caused significant attenuation in the ANG II-induced responses on RBF (-13 +/- 3% vs. -22 +/- 7%), GFR (-19 +/- 5% vs. -33 +/- 3), V (-15 +/- 12% vs. -28 +/- 4%), and U(Na)V (-11 +/- 14% vs. -32 +/- 7%). These data demonstrate that renal responses to ANG II are partly mediated by O2- generation and its interaction with NO. The sodium-retaining effect of ANG II is greatly influenced by O2- generation, particularly in the condition of NO deficiency.

Enhanced Superoxide Activity Modulates Renal Function in NO-Deficient Hypertensive Rats

“…The findings of this present study, as well as our earlier observations, 6,7,16 emphasize an important role of the interaction between O 2 Ϫ and NO in the regulation of renal function and blood pressure. These observations suggest that decreased NO availability can also induce an imbalance between oxidative and antioxidative mechanism in living tissues, which is involved in many pathophysiologic processes in the body.…”

“…Tempol (Sigma) was infused at a dose of 50 g/min per 100 g of body weight. This dose of tempol was selected based on findings in our earlier acute studies in rats 12 and dogs 7,16 that showed significant reductions in the urinary 8-isoprostane excretion rate (U ISO V; marker for endogenous O 2 Ϫ activity). At the midpoint of the clearance collection period, an arterial blood sample was collected from the femoral arterial cannula to measure plasma inulin and sodium concentration.…”

Superoxide Contributes to Development of Salt Sensitivity and Hypertension Induced by Nitric Oxide Deficiency

“…Concentration of 8-isoprostane in urine samples was determined by enzyme immunoassay (Cayman Chemical, Ann Arbor, Mich) 10,18 and H 2 O 2 concentration was measured by colorimetric assay (Cayman Chemical). 20 Nitrate/nitrite (NOx) concentration was also measured colorimetrically (Assay Design, Ann Arbor, Mich). 6,20 To estimate glomerular filtration rate (GFR), creatinine clearance was calculated from the plasma and urine concentration determined colorimetrically.…”

Redox Control of Renal Function and Hypertension

“…In the SHR, tempol decreased both BP and renal vascular resistance (RVR) through NO-mediated mechanisms, whereas shortterm infusions had, in addition, NO-independent effects, likely through inhibition of renal sympathetic nerve activity (373). Reductions in RVR and BP lead to increased diuresis and natriuresis, even when simultaneous NOS blockade is instituted (199). Simultaneous treatment of mice with tempol and Ang II for 2 weeks results in decreased excretion of 8-ISO, prevention of hypertension, and increase in RVR (153).…”