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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
Author(s) -
Husková Zuzana,
Kopkan Libor,
Červenková Lenka,
Doleželová Šárka,
Vaňourková Zdeňka,
Škaroupková Petra,
Nishiyama Akira,
KompanowskaJezierska Elzbieta,
Sadowski Janusz,
Kramer Herbert J.,
Červenka Luděk
Publication year - 2016
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/1440-1681.12553
Subject(s) - endocrinology , medicine , renin–angiotensin system , angiotensin ii , angiotensin converting enzyme , blood pressure , pathophysiology of hypertension , end organ damage , chemistry
Summary 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 ( ACE 2)/angiotensin 1–7 ( ANG 1–7), constitutes an endogenous system counterbalancing the hypertensiogenic axis, ACE /angiotensin II ( ANG II )/ AT 1 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 ACE 2/ 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. ACE 2 inhibitor ( DX 600, 0.2 μ g/day) and ACE 2 activator ( DIZE , 1 mg/day) were administrated via osmotic minipumps. Even though ACE 2 inhibitor significantly decreased and ACE 2 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 ACE 2/ 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 / AT 1 receptor axis.