Diminazene aceturate (DIZE) ameliorates hypertension and induces anxiolytic- and antidepressant-like effects in TGR(Mren2)27

INTRODUCTION: Diminazene aceturate (DIZE) was described as an angiotensin-converting enzyme 2 (ACE2) activator. ACE2/Angiotensin-(1-7)/Mas receptor axis presents protective actions on cardiovascular diseases and plays an important modulatory role in the neurobiology of mood and anxiety disorders. OBJECTIVES: To evaluate the effects of chronic intracerebroventricular (ICV) treatment with DIZE on blood pressure, anxiety- and depression-like behaviors in hypertensive transgenic (mRen2)27 rats (TGR). METHODS: Male TGR and Sprague-Dawley rats (10-12 weeks old) were subjected to chronic ICV infusion of DIZE (1.0 μg/h for 7 days). Blood pressure and heart rate were measured by tail plethysmography and anxiety- and depression-like behaviors were evaluated through elevated plus maze, marble burying and forced swim tests, respectively. RESULTS: Treatment with DIZE induced a significant reduction in mean arterial pressure in both TGR and SD rats. A decrease in heart rate was only observed in the hypertensive animals. Additionally, treatment with DIZE attenuated the anxiety- and depression-like behaviors that were observed in TGR. CONCLUSION: DIZE has central anti-hypertensive, anxiolytic, and anti-depressive effects.