Angiotensin System Modulations in Spontaneously Hypertensive Rats and Consequences on Erythrocyte Properties; Action of MLN-4760 and Zofenopril

Abstract

Various pathologies (COVID-19 including) are associated with abnormalities in erythrocyte properties. Hypertension represents an unfavorable condition for erythrocyte quality and is the most prevalent risk factor in COVID-19 patients. ACE2 downregulation that is typical of these patients can further deteriorate cardiovascular health; however, its consequences on erythrocyte properties are not known yet. The aim was to investigate the effect of ACE2 inhibition and the potential beneficial effect of zofenopril on erythrocytes in spontaneously hypertensive rats. ACE2 inhibition induced by MLN-4760 (1 mg/kg/day for 2 weeks) led to deterioration of erythrocyte morphology and osmotic resistance, but plasma markers of oxidative stress, erythrocyte deformability, nitric oxide production and Na,K-ATPase activity were not significantly affected. Zofenopril administration (10 mg/kg/day, initiated after 4-day-lasting ACE2 inhibition) resulted in unexpected increase in angiotensin II plasma levels in both control and ACE-inhibited spontaneously hypertensive rats, but in normalization of osmotic resistance in ACE2-inhibited rats. The overall effect of zofenopril on erythrocyte qualities could be evaluated as beneficial.

Keywords

• erythrocytes
• SHR
• ACE2
• MLN-4760
• zofenopril
• angiotensin