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This Article Full Text Full Text (PDF) All Versions of this Article: 295/3/F772    most recent 00019.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (4) Citing Articles via Google Scholar Google Scholar Articles by Gonzalez-Villalobos, R. A. Articles by Navar, L. G. Search for Related Content PubMed PubMed Citation Articles by Gonzalez-Villalobos, R. A. Articles by Navar, L. G.

Intrarenal angiotensin II and angiotensinogen augmentation in chronic angiotensin II-infused mice

Department of Physiology and Hypertension and Renal Center of Excellence, Tulane University Health Sciences Center, New Orleans, Louisiana

Submitted 11 January 2008 ; accepted in final form 19 June 2008

The objectives of this study were to determine the effects of chronic angiotensin II (ANG II) infusions on ANG 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 ANG II infusions at doses of 400 or 1,000 ng·kg^–1·min^–1 either alone or with an AT₁R blocker (olmesartan; 3 mg·kg^–1·day^–1) for 12 days. Systolic and mean arterial pressures were determined by tail-cuff plethysmography and radiotelemetry. On day 13, blood and kidneys were collected for ANG II determinations by radioimmunoanalysis and intrarenal angiotensinogen expression studies by quantitative RT-PCR, Western blotting, and immunohistochemistry. ANG II infusions at the low dose elicited progressive increases in systolic blood pressure (135 ± 2.5 mmHg). In contrast, the high dose induced a rapid increase (152 ± 2.5, P < 0.05 vs. controls, 109 ± 2.8). Renal ANG II content was increased by ANG II infusions at the low dose (1,203 ± 253 fmol/g) and the high dose (1,258 ± 173) vs. 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 ANG 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.

telemetry; mouse kidney; hypertension

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