Enhanced superoxide generation modulates renal function in ANG II-induced hypertensive rats.
This study was performed to examine the role of superoxide formation in the regulation of renal hemodynamic and excretory function and to assess its contribution in the pathogenesis of ANG II-dependent hypertension. Renal responses to acute intra-arterial infusion of the O2(-) scavenger tempol (50 microg x min(-1) x 100 g body wt(-1)) with or without catalase (1,500 U x min(-1) x 100 g(-1); both native and polyethylene glycol-catalase), which reduces H2O2, were evaluated in anesthetized male Sprague-Dawley rats treated chronically with ANG II (65 ng/min) for 2 wk and compared with nontreated control rats. In ANG II-treated hypertensive rats, tempol caused increases in medullary (13 +/- 2%), cortical (5 +/- 2%), and total renal blood flow (9 +/- 2%) without altering systemic arterial pressure. There were also increases in glomerular filtration rate (9 +/- 2%), urine flow (17 +/- 4%), and sodium excretion (26 +/- 5%). However, tempol infusion in nontreated normotensive rats did not cause significant changes in any of these renal parameters. Coinfusion of catalase with tempol did not alter the responses observed with tempol alone, indicating that the observed renal responses to tempol in ANG II-treated rats were attributed to its O2(-) scavenging effects without the involvement of H2O2. Tempol infusion also significantly decreased 8-isoprostane excretion in ANG II-treated rats (39 +/- 6%) without changes in H2O2 excretion. However, coinfusion of catalase reduced H2O2 excretion in both ANG II-treated (41 +/- 6%) and nontreated rats (28 +/- 5%). These data demonstrate that enhanced generation of O2(-) modulates renal hemodynamic and tubular reabsorptive function, possibly leading to sodium retention and thus contributing to the pathogenesis of ANG II-induced hypertension.
Kopkan
Libor
L
Dept. of Physiology, Tulane Hypertension and Renal Center of Excellence, Tulane Univ. Health Sciences Center, New Orleans, LA 70112, USA.
Castillo
Alexander
A
Navar
L Gabriel
LG
Majid
Dewan S A
DS
D000804:Angiotensin II; D000818:Animals; D002374:Catalase / Q000008:administration & dosage* / Q000494:pharmacology; D003497:Cyclic N-Oxides / Q000008:administration & dosage / Q000494:pharmacology*; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006977:Hypertension, Renal / Q000139:chemically induced / Q000503:physiopathology*; D007261:Infusions, Intra-Arterial; D028421:Isoprostanes / Q000378:metabolism / Q000652:urine; D007668:Kidney / Q000503:physiopathology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000187:drug effects; D012964:Sodium / Q000652:urine; D013113:Spin Labels; D013481:Superoxides / Q000378:metabolism*
D003497:Cyclic N-Oxides; D028421:Isoprostanes; D013113:Spin Labels; D013481:Superoxides; D000804:Angiotensin II; D012964:Sodium; D002374:Catalase; C001803:tempol