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
PBN-AR
Instytucja
Instytut Medycyny Doświadczalnej i Klinicznej im. Mirosława Mossakowskiego Polskiej Akademii Nauk
Źródłowe zdarzenia ewaluacyjne
Informacje podstawowe
Główny język publikacji
en
Czasopismo
CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY
ISSN
0305-1870
EISSN
1440-1681
Wydawca
WILEY-BLACKWELL
DOI
URL
Rok publikacji
2016
Numer zeszytu
4
Strony od-do
438-449
Numer tomu
43
Identyfikator DOI
Liczba arkuszy
1,41
Słowa kluczowe
en
angiotensin 1–7
angiotensin II a
ngiotensin-converting enzyme type 2
malignant hypertension
renin-angiotensin system
Streszczenia
Język
en
Treść
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.
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Original article
Original article presents the results of original research or experiment.
Inne
System-identifier
PBN-R:722941
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