Combined suppression of the intrarenal and circulating vasoconstrictor renin-ACE-ANG II axis and augmentation of the vasodilator ACE2-ANG 1-7-Mas axis attenuates the systemic hypertension in Ren-2 transgenic rats exposed to chronic hypoxia
Language English Country Czech Republic Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
25194129
DOI
10.33549/physiolres.932842
PII: 932842
Knihovny.cz E-resources
- MeSH
- Angiotensin I blood MeSH
- Angiotensin II blood MeSH
- Peptidyl-Dipeptidase A blood MeSH
- Angiotensin-Converting Enzyme 2 MeSH
- Hypertension blood genetics physiopathology prevention & control MeSH
- Hypoxia complications enzymology physiopathology MeSH
- Blood Pressure MeSH
- Kidney enzymology MeSH
- Disease Models, Animal MeSH
- Peptide Fragments blood MeSH
- Rats, Sprague-Dawley MeSH
- Rats, Transgenic MeSH
- Proto-Oncogene Mas MeSH
- Proto-Oncogene Proteins blood MeSH
- Receptors, G-Protein-Coupled blood MeSH
- Renin-Angiotensin System * MeSH
- Renin blood genetics MeSH
- Signal Transduction MeSH
- Vasodilation * MeSH
- Vasoconstriction * MeSH
- Age Factors MeSH
- Animals MeSH
- Check Tag
- 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
- angiotensin I (1-7) MeSH Browser
- Angiotensin I MeSH
- Angiotensin II MeSH
- Peptidyl-Dipeptidase A MeSH
- Angiotensin-Converting Enzyme 2 MeSH
- Peptide Fragments MeSH
- Proto-Oncogene Mas MeSH
- Proto-Oncogene Proteins MeSH
- Receptors, G-Protein-Coupled MeSH
- Ren2 protein, mouse MeSH Browser
- Renin MeSH
The aim of the present study was to test the hypothesis that chronic hypoxia would aggravate hypertension in Ren-2 transgenic rats (TGR), a well-defined monogenetic model of hypertension with increased activity of endogenous renin-angiotensin system (RAS). Systolic blood pressure (SBP) in conscious rats and mean arterial pressure (MAP) in anesthetized TGR and normotensive Hannover Sprague-Dawley (HanSD) rats were determined under normoxia that was either continuous or interrupted by two weeks´ hypoxia. Expression, activities and concentrations of individual components of RAS were studied in plasma and kidney of TGR and HanSD rats under normoxic conditions and after exposure to chronic hypoxia. In HanSD rats two weeks´ exposure to chronic hypoxia did not alter SBP and MAP. Surprisingly, in TGR it decreased markedly SBP and MAP; this was associated with substantial reduction in plasma and kidney renin activities and also of angiotensin II (ANG II) levels, without altering angiotensin-converting enzyme (ACE) activities. Simultaneously, in TGR the exposure to hypoxia increased kidney ACE type 2 (ACE2) activity and angiotensin 1-7 (ANG 1-7) concentrations as compared with TGR under continuous normoxia. Based on these results, we propose that suppression of the hypertensiogenic ACE-ANG II axis in the circulation and kidney tissue, combined with augmentation of the intrarenal vasodilator ACE2-ANG 1-7 axis, is the main mechanism responsible for the blood pressure-lowering effects of chronic hypoxia in TGR.
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