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(Hypertension. 2009;53:351.)
© 2009 American Heart Association, Inc.

Original Articles Part 2

Angiotensin-Converting Enzyme–Derived Angiotensin II Formation During Angiotensin II–Induced Hypertension

Romer A. Gonzalez-Villalobos; Ryousuke Satou; Dale M. Seth; Laura C. Semprun-Prieto; Akemi Katsurada; Hiroyuki Kobori; L. Gabriel Navar

From the Departments of Physiology (R.A.G.-V., R.S., D.M.S., L.C.S.-P., A.K., H.K., G.L.G.N.) and Cardiology (L.C.S.-P.) and Hypertension and Renal Center of Excellence (R.A.G.-V., R.S., D.M.S., A.K., H.K., G.L.G.N.), Tulane University Health Sciences Center, New Orleans, La.

Correspondence to Romer A. Gonzalez-Villalobos, Department of Physiology, Tulane University Health Sciences Center, 1430 Tulane Ave, SL39, New Orleans, LA 70112. E-mail rgonzale{at}tulane.edu

The extent to which endogenous angiotensin (Ang) II formation is responsible for increasing kidney Ang II content and blood pressure during Ang II–induced hypertension is unknown. To address this, mice were treated with an Ang-converting enzyme (ACE) inhibitor (ACEi) to block endogenous Ang II formation during chronic Ang II infusions. C57BL/6J male mice (8 to 12 weeks) were subjected to Ang II infusions (400 ng/kg per minute) with or without an ACEi (lisinopril, 100 mg/L in the drinking water) for 12 days. Blood pressure was monitored by tail-cuff method and telemetry. Ang II content was determined by radioimmunoanalysis. Ang II infusions increased 24-hour mean arterial pressure significantly (141.0±3.7 mm Hg) versus controls (110.0±1.0 mm Hg). ACEi prevented the increase in concentration in Ang II–infused mice (Ang II+ACEi; 114.0±7.4 mm Hg; P value not significant). Plasma Ang II content was significantly increased by Ang II (367±60 fmol/mL) versus controls (128±22 fmol/mL; P<0.05); plasma Ang II was not altered by ACEi alone (90±31) or in combination with Ang II infusions (76±27). Intrarenal Ang II content was significantly increased by Ang II (998±143 fmol/g) versus controls (524±60 fmol/g; P<0.05), and this was prevented by ACEi (Ang II+ACEi; 484±102 fmol/g; P value not significant). Thus, ACEi ameliorates the increases in blood pressure and intrarenal Ang II content caused by Ang II infusions, indicating that endogenous ACE-mediated Ang II formation plays a significant role in the increases of blood pressure and intrarenal Ang II during Ang II–induced hypertension.

Key Words: kidney • renin-angiotensin system • ACE inhibitor • telemetry • mice • angiotensin II