Background:
The common antihypertensive angiotensin-converting enzyme (ACE) inhibitor captopril was reported to possess antioxidant and anti-inflammatory effects in different experimental models, diabetic vascular complications arises from increased vascular endothelial inflammation and oxidative stress as well as decreased nitric oxide bioavailability in the vessel walls due to poor glycemic control.
Objective:
This study aimed to evaluate the role of captopril and gliclazide in decreasing diabetes mellitus (DM) vascular
complications caused by decreased cellular glucose uptake and impaired endothelial nitric oxide metabolism, as well as examine the effect of combination on diabetic renal complication and plasma lipid profile.
Materials and methods:
Adult male Wister rats received captopril (25 mg/kg/day) and/or gliclazide (10 mg/kg/day) by oral
gavage daily for one month after induction of DM using streptozotocin (50 mg/kg, i.p., once). Serum glucose and insulin
levels, inflammatory mediatory like TNF-α, oxidative stress biomarkers like glutathione and nitric oxide, and plasma lipid
profile were measured. Besides, histopathological examination of thoracic aorta and kidney tissues, while Western blot assessed the expression of nitric oxide synthase (NOS) subtypes in the thoracic aorta.
Results:
Captopril significantly improved vascular architecture and oxidative stress and modulated nitric oxide synthesis via
regulation of nitric oxide synthases, as well as decreased inflammation via down-regulating TNF-α, decreased systolic and
diastolic blood pressure and improved serum lipid profile in diabetic rats. Gliclazide increased serum insulin and decreased
serum glucose, as well as its antioxidant and anti-inflammatory effects.
Discussion and conclusions:
Captopril showed a promising protective effect against DM vascular complications, at least
via nitric oxide modulating effect, antioxidant effect and anti-inflammatory activity that appeared in biochemical and histopathological findings, lipid profile, renal function and architecture improvements. Combining gliclazide with captopril gives
an additive effect through enhanced glycemic control and increased anti-oxidant and anti-inflammatory properties above
captopril alone.