Superoxide scavenging attenuates renal responses to ANG II during nitric oxide synthase inhibition in anesthetized dogs.
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.
Department of Physiology, Tulane University Health Sciences Center, New Orleans, LA 70112, USA. majid@tulane.edu
Dewan S A
DS
Majid
Akira
A
Nishiyama
Keith E
KE
Jackson
Alexander
A
Castillo
D000804:Angiotensin II / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D004285:Dogs; D005260:Female; D016166:Free Radical Scavengers; D005919:Glomerular Filtration Rate; D007261:Infusions, Intra-Arterial; D008297:Male; D009569:Nitric Oxide / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D013481:Superoxides / Q000494:pharmacology*; D014662:Vasoconstrictor Agents / Q000008:administration & dosage / Q000494:pharmacology*
D016166:Free Radical Scavengers; D014662:Vasoconstrictor Agents; D013481:Superoxides; D000804:Angiotensin II; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase