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

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. (Hypertension. 2009; 53[part 2]: 351-355.)