Role of renal perfusion pressure versus angiotensin II on renal oxidative stress in angiotensin II-induced hypertensive rats.
Renal oxidative stress is thought to contribute to both the etiology and the associated renal injury in angiotensin (Ang) II-dependent hypertension. The contribution of Ang II versus elevated renal perfusion pressure (RPP) on albuminuria and renal oxidative stress in this model of hypertension was explored in the present study by chronically servocontrolling RPP to the left kidney and comparing responses with the right uncontrolled kidney and the left kidney of sham rats. Hypertension was produced in Sprague-Dawley rats fed a 4% NaCl diet by chronic IV infusion of Ang II (25 ng/kg per minute). The RPP to the left kidney was servocontrolled to mean daily pressures averaging approximately 120 mm Hg, whereas the uncontrolled kidneys averaged approximately 170 mm Hg over 14 days of Ang II infusion. Ang II infusion resulted in a 2.4-fold increase in albuminuria, which was RPP dependent. Kidneys exposed to both elevated RPP and Ang II (uncontrolled kidneys) displayed a 3.5-fold increase in malondialdehyde excretion and a 37% and 27% increase in renal cortical and outer medullary superoxide production, respectively. Elevated RPP significantly contributed to global renal oxidative stress (70% increase in malondialdehyde excretion) and outer medullary superoxide production. Elevated circulating levels of Ang II, per se, were responsible for a 1.5-fold and 2.0-fold increase in renal cortical and outer medullary NADPH oxidase activity, respectively. In summary, this study demonstrates that elevated RPP is directly responsible for the excess albuminuria in Ang II-infused rats, whereas both elevated RPP and Ang II directly contribute to the observed renal oxidative stress.
Polichnowski
Aaron J
AJ
Department of Physiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
Jin
Chunhua
C
Yang
Chun
C
Cowley
Allen W
AW
D000419:Albuminuria / Q000503:physiopathology; D000704:Analysis of Variance; D000804:Angiotensin II / Q000009:adverse effects / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004195:Disease Models, Animal; D006977:Hypertension, Renal / Q000139:chemically induced / Q000503:physiopathology*; D007262:Infusions, Intravenous; D007672:Kidney Cortex / Q000187:drug effects / Q000473:pathology; D007677:Kidney Function Tests; D007679:Kidney Medulla / Q000187:drug effects / Q000473:pathology; D016014:Linear Models; D008297:Male; D008315:Malondialdehyde / Q000652:urine; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D011336:Probability; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D012079:Renal Circulation / Q000187:drug effects / Q000502:physiology; D013481:Superoxides / Q000378:metabolism; D016482:Urinalysis; D014662:Vasoconstrictor Agents / Q000009:adverse effects / Q000494:pharmacology*
D014662:Vasoconstrictor Agents; D013481:Superoxides; D000804:Angiotensin II; D008315:Malondialdehyde
Hypertension. 1992 May;19(5):464-74
1568765
Hypertension. 2001 Sep;38(3 Pt 2):655-9
11566950
J Am Soc Nephrol. 2003 Nov;14(11):2902-7
14569100
Science. 1996 May 3;272(5262):676-80
8614826
Hypertension. 2008 Feb;51(2):488-93
18158344
Kidney Int. 2000 Jul;58(1):144-52
10886559
Am J Physiol Renal Physiol. 2007 Mar;292(3):F993-8
17132867
Kidney Int. 1998 Sep;54(3):687-97
9734594
Am J Physiol Renal Physiol. 2006 Dec;291(6):F1308-14
16788142
Circulation. 2003 Sep 9;108(10):1253-8
12874194
Kidney Int. 1994 Feb;45(2):369-76
8164421
Hypertension. 2000 Jan;35(1 Pt 2):476-9
10642344
J Am Soc Nephrol. 2005 Dec;16(12):3631-41
16236804
Am J Physiol Renal Physiol. 2006 Aug;291(2):F350-7
16597609
Hypertension. 2009 Jun;53(6):1048-53
19433780
Hypertension. 2008 Nov;52(5):777-86
18852392
Kidney Int Suppl. 2003 Oct;(86):S27-32
12969124
Circ Res. 1998 Jun 1;82(10):1094-101
9622162
Hypertension. 2009 Dec;54(6):1269-77
19858406
Clin Drug Investig. 2009;29(6):419-25
19432501
Circ Res. 2003 Jan 10;92(1):23-31
12522117
Hypertension. 2004 Apr;43(4):752-9
14981064
Am J Physiol Renal Physiol. 2009 May;296(5):F1052-60
19261744
Am J Physiol Heart Circ Physiol. 2005 Jan;288(1):H22-8
15598867
J Am Soc Nephrol. 2008 Aug;19(8):1472-82
18417720
Circ Res. 1994 Apr;74(4):700-9
7511072
Am J Physiol. 1993 Mar;264(3 Pt 2):R578-83
8457011
Physiol Rev. 2003 Jan;83(1):253-307
12506131
Am J Physiol Regul Integr Comp Physiol. 2003 Jul;285(1):R117-24
12609817
Hypertension. 2008 Dec;52(6):1084-90
18981330
Curr Med Res Opin. 2009 Sep;25(9):2271-80
19627177
J Am Soc Nephrol. 2001 Mar;12(3):413-422
11181788
Am J Physiol Regul Integr Comp Physiol. 2003 May;284(5):R1219-30
12676744
Exp Nephrol. 2001;9(6):360-5
11701994
JAMA. 1996 May 22-29;275(20):1581-9
8622250
Hypertension. 2006 Apr;47(4):692-8
16505210
Clin J Am Soc Nephrol. 2006 Sep;1(5):1054-65
17699327