Key result
Pharmacological inhibition or activation of the ACE2/ANG 1-7 complex did not significantly alter blood pressure, albuminuria, cardiac hypertrophy, or renal glomerular damage in transgenic rats.
Why the study?
Does pharmacological modulation of the ACE2/ANG 1-7 complex alter blood pressure and end-organ damage in a rat model of ANG II-dependent malignant hypertension?
Does pharmacological modulation of the ACE2/ANG 1-7 complex alter blood pressure and end-organ damage in a rat model of ANG II-dependent malignant hypertension?
Pharmacological modulation of the intrarenal ACE2/ANG 1-7 complex does not alter the course of ANG II-dependent malignant hypertension in a transgenic rat model.
Does not support targeting ACE2/ANG 1-7 in this model; leaves open its relevance in human hypertension or other systems.
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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Husková et al. (2016) studied ANG II-dependent malignant hypertension. ACE2 inhibitor (DX 600) and ACE2 activator (DIZE) was evaluated on Blood pressure, albuminuria, cardiac hypertrophy and renal glomerular damage. Pharmacological inhibition or activation of the ACE2/ANG 1-7 complex did not significantly alter blood pressure, albuminuria, cardiac hypertrophy, or renal glomerular damage in transgenic rats.
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