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Intrarenal RAS expression during Ang II‐infusions and ACE inhibition
Author(s) -
GonzalezVillalobos Romer A.,
Satou Ryousuke,
SemprunPrieto Laura C.,
Ohashi Naro,
Katsurada Akemi,
Upchurch G. Michael,
PrietoCarrasquero Minolfa C.,
Kobori Hiroyuki,
Navar L. Gabriel
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.606.11
Subject(s) - endocrinology , medicine , immunohistochemistry , lisinopril , renin–angiotensin system , western blot , angiotensin ii , ace inhibitor , chemistry , angiotensin converting enzyme , receptor , blood pressure , gene , biochemistry
ACE inhibition (ACEi) ameliorates the development of hypertension and the intrarenal Ang II augmentation observed during chronic Ang II infusions in mice, the objective of this study was to determine if these effects are associated with changes in the mouse intrarenal RAS. 9‐12 week C57BL/6J male mice were distributed as follows: controls (n=10), Ang II‐infused (Ang II=8, 400 ng/kg/min), controls + ACEi (ACEi=10, lisinopril, 100 mg/L) and Ang II‐infused + ACEi (Ang II + ACEi=11). As previously reported, ACEi attenuated the increases in MAP (monitored by telemetry) and intrarenal Ang II caused by Ang II infusions (measured by RIA). No significant changes were observed in angiotensinogen (AGT), ACE or AT 1 R mRNA by qRT‐PCR. AGT protein expression [determined by Western blot (WB) and Immunohistochemistry (IHC)] was increased by Ang II infusions (Ang II, 1.41 ± 0.14 by WB, 2.5‐fold increase by IHC) vs. controls (1.00, p <0.05) and this was prevented by ACEi (ACEi + Ang II, 0.80 ± .07 by WB, NS). Tubular renin protein increased in ACEi‐treated mice (ACEi, 2.3 ± 0.36; Ang II + ACEi, 4.01 ± 1.1 by IHC) vs. controls (1.00, p <0.05), but was not altered by Ang II alone. ACE protein was increased by Ang II (Ang II, 1.3 ± 0.18 by IHC) vs. controls (1.00, p <0.05) and ACEi prevented this changes (Ang II + ACEi, 0.85 ± 0.11). AT 1 R protein was increased by Ang II infusions (Ang II, 1.27 ± 0.06 by WB) vs. controls (1.00 p <0.05) and this was prevented by ACEi (Ang II + ACEi, 1.14 ± 0.06, NS). In summary, Ang II infusions augmented the expression of intrarenal AGT, ACE and the AT 1 R and did not suppress tubular renin. The findings that these changes are prevented by ACEi suggest that they are mediated by endogenous ACE‐derived Ang II.