Intrarenal alterations of the angiotensin-converting enzyme type 2/angiotensin 1-7 complex of the renin-angiotensin system do not alter the course of malignant hypertension in Cyp1a1-Ren-2 transgenic rats
Language English Country Australia Media print
Document type Journal Article, Research Support, Non-U.S. Gov't
- Keywords
- angiotensin 1-7, angiotensin II, angiotensin-converting enzyme type 2, malignant hypertension, renin-angiotensin system,
- MeSH
- Enzyme Activators pharmacology MeSH
- Albuminuria complications MeSH
- Angiotensin I metabolism MeSH
- Peptidyl-Dipeptidase A metabolism MeSH
- Angiotensin-Converting Enzyme 2 MeSH
- Cytochrome P-450 CYP1A1 genetics MeSH
- Diminazene analogs & derivatives pharmacology MeSH
- Hypertension, Malignant complications metabolism physiopathology urine MeSH
- Blood Pressure drug effects MeSH
- Rats MeSH
- Kidney drug effects metabolism MeSH
- Mice MeSH
- Peptide Fragments metabolism MeSH
- Peptides pharmacology MeSH
- Rats, Transgenic MeSH
- Gene Expression Regulation drug effects MeSH
- Renin-Angiotensin System drug effects MeSH
- Renin genetics MeSH
- Sodium urine MeSH
- Body Weight drug effects MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Ace2 protein, mouse MeSH Browser
- Ace2 protein, rat MeSH Browser
- Enzyme Activators MeSH
- angiotensin I (1-7) MeSH Browser
- Angiotensin I MeSH
- Peptidyl-Dipeptidase A MeSH
- Angiotensin-Converting Enzyme 2 MeSH
- Cytochrome P-450 CYP1A1 MeSH
- Diminazene MeSH
- diminazene aceturate MeSH Browser
- DX600 peptide MeSH Browser
- Peptide Fragments MeSH
- Peptides MeSH
- Ren2 protein, mouse MeSH Browser
- Renin MeSH
- Sodium MeSH
The role of the intrarenal renin-angiotensin system (RAS) in the pathophysiology of malignant hypertension is not fully understood. Accumulating evidence indicates that the recently discovered vasodilator axis of the RAS, angiotensin-converting enzyme (ACE) type 2 (ACE2)/angiotensin 1-7 (ANG 1-7), constitutes an endogenous system counterbalancing the hypertensiogenic axis, ACE/angiotensin II (ANG II)/AT1 receptor. This study aimed to evaluate the role of the intrarenal vasodilator RAS axis in the pathophysiology of ANG II-dependent malignant hypertension in Cyp1a1-Ren-2 transgenic rats. ANG II-dependent malignant hypertension was induced by 13 days' dietary administration of indole-3-carbinol (I3C), a natural xenobiotic that activates the mouse renin gene in Cyp1a1-Ren-2 transgenic rats. It was hypothesized that pharmacologically-induced inhibition of the ACE2/ANG 1-7 complex should aggravate, and activation of this axis should attenuate, the course of ANG II-dependent malignant hypertension. Blood pressure (BP) was monitored by radiotelemetry. ACE2 inhibitor (DX 600, 0.2 μg/day) and ACE2 activator (DIZE, 1 mg/day) were administrated via osmotic minipumps. Even though ACE2 inhibitor significantly decreased and ACE2 activator increased intrarenal ANG 1-7 concentrations, the course of BP, as well as of albuminuria, cardiac hypertrophy and renal glomerular damage, were not altered. It was shown that intrarenal alterations in the ACE2/ANG 1-7 complex did not significantly modify the course of malignant hypertension in I3C-induced Cyp1a1-Ren-2 transgenic rats. Thus, in our experimental setting alterations of this intrarenal vasodilator complex of the RAS do not significantly modify the form of malignant hypertension that clearly depends on the inappropriately increased activity of the ACE/ANG II/AT1 receptor axis.
Department of Pathophysiology 2nd Faculty of Medicine Charles University Prague Czech Republic
Department of Pharmacology Kagawa University Kagawa Japan
Section of Nephrology Department of Medicine University of Bonn Bonn Germany
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