Evaluation of anticonvulsant activity of angiotensin receptor antagonists in an animal model

Background: Epilepsy is common chronic disorder in clinical practice and there was some studies which shows brain renin angiotensin system may be involved in upregulation of seizures hence present study was planned to investigate whether angiotensin II AT1 receptor antagonists possess anticonvulsant activity in experimental animals.Methods: The anticonvulsant activity of angiotensin receptor antagonists, losartan (50 mg/kg), telmisartan (30 mg/kg) and candesartan (20 mg/kg), were administered intraperitoneally to the mice and evaluated by using maximum electroshock (MES) and pentylenetetrazol induced seizures (PTZ) seizure methods. The standard was taken as phenytoin for MES and diazepam for PTZ method. Motor impairment of performance was assessed by the inverted screen test and spontaneous motor activity with digital actophotometer.Results: Losartan demonstrated the anticonvulsant efficacy in MES and PTZ models. Telmisartan and candesartan have anticonvulsant activity in MES induced seizures, but did not show protection against pentylenetetrazol induced seizures. Losartan at dose 50 mg/kg prolonged the mean latency to convulsion (p<0.01) and mean number of convulsions also significantly reduced (p<0.05) convulsions in the mice. Telmisartan and candesartan at dose 30 mg/kg and 20 mg/kg respectively showed significant prolongation in mean latency to convulsion (p<0.05). None of the test drugs i.e. angiotensin receptor antagonists showed significant motor impairment.Conclusions: Angiotensin receptor antagonists: losartan, telmisartan and candesartan had showed anticonvulsant activity in PTZ and MES seizure methods. The exact mechanism of action of their anticonvulsant action not precisely known and hence there is more studies need to test it in various other animal anticonvulsant models.

Debatable points of using angiotensin-converting enzyme inhibitors and angiotensin receptor antagonists in patients with COVID-19

The COVID-19 pandemic is a serious threat to global health. The infection mechanism is the binding of SARS-CoV-2 to angiotensin-converting enzyme 2 (ACE2) and internalization of the complex by the host cell. ACE inhibitors/angiotensin receptor antagonists (ARA) are known to increase ACE2 expression and are recommended for the treatment of many cardiovascular diseases (CVD). Thus, it has been suggested that treatment with renin-angiotensin-aldosterone system blockers (RAAS) increases the viral load and the risk of severe acute respiratory distress syndrome. However, ACE2 also converts angiotensin II into substances with cardioprotective effects. In addition, there is no evidence that RAAS inhibitors increase the severity of COVID-19 infection, while the risks of withdrawal of ACE inhibitors/ARA in patients with CVD are proven. There is also no evidence to support the idea that the administration of ACE inhibitors/ARA promotes the coronavirus’s penetration by increasing the ACE2 expression. According to the guidelines of the Russian Society of Cardiology and the consensus statements of international cardiology societies, it is necessary to continue taking RAAS inhibitors in high-risk patients with COVID-19. This review provides an analysis of foreign articles revealing the pathophysiological pathways and recommendations for using ACE inhibitors/ARA in patients with CVD and COVID-19 infection.