Key result
The ACE2 activator diminazene aceturate (DIZE) significantly reduced mean pulmonary arterial pressure, left atrial pressure, and pulmonary vascular remodeling in a rat model of pulmonary hypertension secondary to left ventricular dysfunction.
Why the study?
Pulmonary hypertension lacks definitive therapy, and the role of the ACE2 activator diminazene aceturate in pulmonary hypertension secondary to left ventricular dysfunction required investigation.
Does diminazene aceturate improve hemodynamics and vascular remodeling in a rat model of pulmonary hypertension secondary to left ventricular dysfunction?
Does diminazene aceturate improve hemodynamics and vascular remodeling in a rat model of pulmonary hypertension secondary to left ventricular dysfunction?
Activation of ACE2 with diminazene aceturate prevents and reverses pulmonary hypertension secondary to left ventricular dysfunction in a rat model.
Pulmonary hypertension (PH) is a lethal and rapidly progressing disorder if left untreated, but there is still no definitive therapy. An imbalance between vasoconstriction and vasodilation has been proposed as the mechanism underlying PH. Among the vasomediators of the pulmonary circulation is the renin-angiotensin system (RAS), the involvement of which in the development of PH has been proposed. Within the RAS, angiotensin-converting enzyme 2 (ACE2), which converts angiotensin (Ang) II into Ang-(1-7), is an important regulator of blood pressure, and has been implicated in cardiovascular disease and PH. In this study, we investigated the effects of the ACE2 activator diminazene aceturate (DIZE) on the development of PH secondary to left ventricular dysfunction. A model of PH secondary to left ventricular dysfunction was established in 6-week-old Wistar rats by ascending aortic banding for 42 days. The hemodynamics and pulmonary expression of ACE, Ang II, ACE2, Ang-(1-7), and the Ang-(1-7) MAS receptor were investigated in the early treatment group, which was administered DIZE (15 mg/kg/day) from days 1 to 42, and in the late treatment group, administered DIZE (15 mg/kg/day) from days 29 to 42. Sham-operated rats served as controls. DIZE ameliorated mean pulmonary artery pressure, pulmonary arteriolar remodeling, and plasma brain natriuretic peptide levels, in addition to reversing the overexpression of ACE and up-regulation of both Ang-(1-7) and MAS, in the early and late treatment groups. DIZE has therapeutic potential for preventing the development of PH secondary to left ventricular dysfunction through ACEII activation and the positive feedback of ANG-(1-7) on the MAS receptor. A translational study in humans is needed to substantiate these findings.
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Chen et al. (2020) studied Pulmonary hypertension secondary to left ventricular dysfunction. Diminazene aceturate (DIZE) vs. Saline (vehicle) was evaluated on Mean pulmonary arterial pressure (PAP) (p=<0.05). The ACE2 activator diminazene aceturate (DIZE) significantly reduced mean pulmonary arterial pressure, left atrial pressure, and pulmonary vascular remodeling in a rat model of pulmonary hypertension secondary to left ventricular dysfunction.
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