Effect of Captopril on Some Peptides of Renin Angiotensin System (RAS) in Plasmodium berghei-Infected Mice

Abstract

Aim: There are conflicting reports on the effect of peptides of the Renin Angiotensin System (RAS) on the pathogenesis of malaria infection. Captopril is a common antihypertensive drug that inhibits angiotensin-converting enzyme (ACE), a critical peptide of RAS, and its effect on the pathological process of malaria is just beginning to unfold. This study was carried out to investigate the effect of captopril on parasitemia, ACE, angiotensin II, and angiotensin II type 1 receptor (AT1R) levels in Plasmodium berghei-infected mice. Methodology: Twenty-five mice divided into: Group 1 (control), Group 2 (Malaria control), Groups 3, 4 and 5 (Treated with 0.03 mg/kg lonart, 0.03 and 0.09 mg/kg captopril, respectively) were treated for 14 days. On the 15th day, they were sacrificed to obtain the blood and kidneys. The concentration of ACE and Ang II in serum and kidneys; and expression of ACE and AT1R in kidneys were assayed using standard protocols. Results: There was a significant decrease (P<0.05) in parasitemia in all treated mice compared to malaria control mice, and by the 14th day, the parasitemia level in mice given 0.09 mg/kg captopril and 0.03 mg/kg lonart was not different (P>0.05) from control. The ACE and angiotensin II levels in serum and kidneys of malaria-infected mice increased significantly (P<0.05), but decreased (P<0.05) when given 0.03 mg/kg lonart, and both doses of captopril. With respect to gene expression, the ACE and AT1R mRNA were upregulated (P<0.05) in the kidneys of diseased mice, but treatment with captopril resulted in a dose-dependent decrease (P<0.05). Conclusion: Captopril inhibits Plasmodium parasite; and this may be due to its ability to down-regulate ACE and AT1R expression.