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1 Department of Physiology and Hypertension and Renal Center of Excellence, Tulane University Health Sciences Center, New Orleans, Louisiana, United States
* To whom correspondence should be addressed. E-mail: rgonzale{at}tulane.edu.
The objectives of this study were to determine the effects of chronic angiotensin II infusions on angiotensin II content and angiotensinogen expression in the mouse kidney and the role of the angiotensin II type 1 receptor (AT1R) in mediating these changes. C57BL/6J male mice were subjected to angiotensin II infusions at doses of 400 or 1000 ng/kg/min either alone or with an AT1R blocker (Olmesartan 3 mg/kg/d) for 12 days. Systolic and mean arterial pressures (SBP and MAP) were determined by tail-cuff plethysmography and radiotelemetry. On day 13, blood and kidneys were collected for angiotensin II determinations by radioimmunoanalysis and intrarenal angiotensinogen expression studies by qRT-PCR, Western blot and immunohistochemistry. Angiotensin II infusions at the low dose elicited progressive increases in SBP (135±2.5 mmHg). In contrast, the high dose induced a rapid increase (152±2.5) (p<0.05 versus controls, 109±2.8). Renal angiotensin II content was increased by angiotensin II infusions at the low dose (1203±253 fmol/g) and the high dose (1258±173) versus controls (499±40, p<0.05). Kidney angiotensinogen mRNA and protein were increased only by the low dose to 1.13±0.02 and 1.26±0.10 respectively over controls (1.00, p<0.05). These effects were not observed in mice infused at the high dose and those receiving olmesartan. The results indicate that chronic Ang II infusions augment mouse intrarenal angiotensin II content with AT1R-dependent uptake occurring at both doses, but only the low dose of infusion, which elicited a slow progressive response, causes an AT1R-dependent increase in intrarenal angiotensinogen expression.
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