title: Role of renal perfusion pressure versus angiotensin II on renal oxidative stress in angiotensin II-induced hypertensive rats.
abstract: 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.
authors.affiliation: Department of Physiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
authors.forename: Aaron J
authors.initials: AJ
authors.lastname: Polichnowski
authors.forename: Chunhua
authors.initials: C
authors.lastname: Jin
authors.forename: Chun
authors.initials: C
authors.lastname: Yang
authors.forename: Allen W
authors.initials: AW
authors.lastname: Cowley
mesh_terms: 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*
chemical_list: D014662:Vasoconstrictor Agents; D013481:Superoxides; D000804:Angiotensin II; D008315:Malondialdehyde
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