1. Intrarenal mouse renin-angiotensin system during ANG II-induced hypertension and ACE inhibition
- Author
-
Gonzalez-Villalobos, Romer A., Satou, Ryousuke, Ohashi, Naro, Semprun-Prieto, Laura C., Katsurada, Akemi, Kim, Catherine, Upchurch, G. M., Prieto, Minolfa C., Kobori, Hiroyuki, and Navar, L. Gabriel
- Abstract
Angiotensin-converting enzyme (ACE) inhibition (ACEi) ameliorates the development of hypertension and the intrarenal ANG II augmentation in ANG II-infused mice. To determine if these effects are associated with changes in the mouse intrarenal renin-angiotensin system, the expression of angiotensinogen (AGT), renin, ACE, angiotensin type 1 receptor (AT1R) mRNA (by quanitative RT-PCR) and protein [by Western blot (WB) and/or immunohistochemistry (IHC)] were analyzed. C57BL/6J male mice (9–12 wk old) were distributed as controls (n= 10), ANG II infused (ANG II = 8, 400 ng·kg−1·min−1for 12 days), ACEi only (ACEi = 10, lisinopril, 100 mg/l), and ANG II infused + ACEi (ANG II + ACEi = 11). When compared with controls (1.00), AGT protein (by WB) was increased by ANG II (1.29 ± 0.13, P< 0.05), and this was not prevented by ACEi (ACEi + ANG II, 1.31 ± 0.14, P< 0.05). ACE protein (by WB) was increased by ANG II (1.21 ± 0.08, P< 0.05), and it was reduced by ACEi alone (0.88 ± 0.07, P< 0.05) or in combination with ANG II (0.80 ± 0.07, P< 0.05). AT1R protein (by WB) was increased by ANG II (1.27 ± 0.06, P< 0.05) and ACEi (1.17 ± 0.06, P< 0.05) but not ANG II + ACEi [1.15 ± 0.06, not significant (NS)]. Tubular renin protein (semiquantified by IHC) was increased by ANG II (1.49 ± 0.23, P< 0.05) and ACEi (1.57 ± 0.15, P< 0.05), but not ANG II + ACEi (1.10 ± 0.15, NS). No significant changes were observed in AGT, ACE, or AT1R mRNA. In summary, reduced responses of intrarenal tubular renin, ACE, and the AT1R protein to the stimulatory effects of chronic ANG II infusions, in the presence of ACEi, are associated with the effects of this treatment to ameliorate augmentations in blood pressure and intrarenal ANG II content during ANG II-induced hypertension.
- Published
- 2010
- Full Text
- View/download PDF