Pressure-Induced Renal Injury in Angiotensin II Versus Norepinephrine-Induced Hypertensive Rats

• Published in: Hypertension (Dallas, Tex. 1979) Tex. 1979), 2009-12, Vol.54 (6), p.1269-1277
• Main Authors: Polichnowski, Aaron J, Cowley, Allen W
• Format: Article
• Language: English
• Subjects: Angiotensin II - pharmacology; Animals; Arterial hypertension. Arterial hypotension; Biological and medical sciences; Blood and lymphatic vessels; Blood Pressure - drug effects; Cardiology. Vascular system; Catheterization; Disease Models, Animal; Experimental diseases; Fibrosis; Glomerulosclerosis, Focal Segmental - chemically induced; Glomerulosclerosis, Focal Segmental - pathology; Glomerulosclerosis, Focal Segmental - physiopathology; Heart Rate - drug effects; Hypertension, Renal - chemically induced; Hypertension, Renal - pathology; Hypertension, Renal - physiopathology; Kidney Cortex Necrosis - chemically induced; Kidney Cortex Necrosis - pathology; Kidney Cortex Necrosis - physiopathology; Male; Medical sciences; Norepinephrine - pharmacology; Rats; Rats, Sprague-Dawley; Renal Artery - physiology; Sodium Chloride, Dietary - pharmacology; Vasoconstrictor Agents - pharmacology
• ISSN: 0194-911X; 1524-4563
• DOI: 10.1161/HYPERTENSIONAHA.109.139287

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 μg/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.