Pressure-induced renal injury in angiotensin II versus norepinephrine-induced hypertensive rats.
The susceptibility to renal perfusion pressure (RPP)-induced renal injury was investigated in angiotensin II (Ang II)- versus norepinephrine (NE)-infused hypertensive rats. To determine the magnitude of RPP-induced injury, Sprague-Dawley rats fed a 4% salt diet were instrumented with a servocontrolled aortic balloon occluder positioned between the renal arteries to maintain RPP to the left kidney at baseline levels whereas the right kidney was exposed to elevated RPP during a 2-week infusion of Ang II IV (25 ng/kg per minute), NE IV (0.5, 1.0, and 2.0 microg/kg per minute on days 1, 2, and 3 to 14, respectively), or saline IV (sham rats). Over the 14 days of Ang II infusion, RPP averaged 161.5+/-8.0 mm Hg to uncontrolled kidneys and 121.9+/-2.0 mm Hg to servocontrolled kidneys. In NE-infused rats, RPP averaged 156.3+/-3.0 mm Hg to uncontrolled kidneys and 116.9+/-2.0 mm Hg to servocontrolled kidneys. RPP averaged 111.1+/-1.0 mm Hg to kidneys of sham rats. Interlobular arterial injury and juxtamedullary glomerulosclerosis were largely RPP dependent in both models of hypertension. Superficial cortical glomerulosclerosis was greater and RPP dependent in NE- versus Ang II-infused rats, which was primarily independent of RPP. Outer medullary tubular necrosis and interstitial fibrosis were also primarily RPP dependent in both models of hypertension; however, the magnitude of injury was exacerbated in Ang II-infused rats. We conclude that elevated RPP is the dominant cause of renal injury in both NE- and Ang II-induced hypertensive rats and that underlying neurohumoral factors in these models of hypertension alter the pattern and magnitude of RPP-induced renal injury.
Department of Physiology, Medical College of Wisconsin, 8701 Watertown Plank Rd, Milwaukee, WI 53226, USA.
Aaron J
AJ
Polichnowski
Allen W
AW
Cowley
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002404:Catheterization; D004195:Disease Models, Animal; D005355:Fibrosis; D005923:Glomerulosclerosis, Focal Segmental / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D006977:Hypertension, Renal / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology*; D007673:Kidney Cortex Necrosis / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012077:Renal Artery / Q000502:physiology; D017673:Sodium Chloride, Dietary / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D017673:Sodium Chloride, Dietary; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D009638:Norepinephrine