title: 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.
abstract: 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.
authors.affiliation: Department of Pathophysiology, Second Faculty of Medicine, Charles University, Prague, Czech Republic. luce@medicon.cz.
authors.forename: L
authors.initials: L
authors.lastname: Červenka
authors.forename: J
authors.initials: J
authors.lastname: Bíbová
authors.forename: Z
authors.initials: Z
authors.lastname: Husková
authors.forename: Z
authors.initials: Z
authors.lastname: Vaňourková
authors.forename: H J
authors.initials: HJ
authors.lastname: Kramer
authors.forename: J
authors.initials: J
authors.lastname: Herget
authors.forename: Š
authors.initials: Š
authors.lastname: Jíchová
authors.forename: J
authors.initials: J
authors.lastname: Sadowski
authors.forename: V
authors.initials: V
authors.lastname: Hampl
mesh_terms: D000367:Age Factors; D000803:Angiotensin I / Q000097:blood*; D000804:Angiotensin II / Q000097:blood*; D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D001794:Blood Pressure; D004195:Disease Models, Animal; D006973:Hypertension / Q000097:blood / Q000235:genetics / Q000503:physiopathology / Q000517:prevention & control*; D000860:Hypoxia / Q000150:complications* / Q000201:enzymology / Q000503:physiopathology; D007668:Kidney / Q000201:enzymology*; D010446:Peptide Fragments / Q000097:blood*; D007703:Peptidyl-Dipeptidase A / Q000097:blood*; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000097:blood*; D017207:Rats, Sprague-Dawley; D055647:Rats, Transgenic; D043562:Receptors, G-Protein-Coupled / Q000097:blood*; D012083:Renin / Q000097:blood* / Q000235:genetics; D012084:Renin-Angiotensin System; D015398:Signal Transduction; D014661:Vasoconstriction; D014664:Vasodilation
chemical_list: D010446:Peptide Fragments; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D043562:Receptors, G-Protein-Coupled; C473112:Ren2 protein, mouse; D000804:Angiotensin II; D000803:Angiotensin I; D007703:Peptidyl-Dipeptidase A; C000705328:Ace2 protein, mouse; C000705329:Ace2 protein, rat; D000085962:Angiotensin-Converting Enzyme 2; D012083:Renin; C118790:angiotensin I (1-7)