An
angiotensin 2 type 1 receptor blocker,
olmesartan, and a
calcium channel blocker,
azelnidipine, possess not only an
antihypertensive effect but also an antioxidative effect and other beneficial effects. In the present study, we examined the efficacy of
olmesartan and
azelnidipine monotherapy (2 mg/kg or 10 mg/kg each) and their combination
therapy (1 mg/kg each) on
stroke-prone spontaneously hypertensive rats (SHR-SP) in relation to oxidative stress,
inflammation, and the neurovascular unit. In comparison with the vehicle group,
body weight, regional cerebral blood flow, and motor function were preserved, whereas systolic blood pressure and diastolic blood pressure decreased in the five
drug-treatment groups. Spontaneous
infarct volume decreased with the low-dose combination of
olmesartan plus
azelnidipine and with the high-dose
olmesartan, with a further decrease in the high-dose
azelnidipine group. In addition, these drugs dose-dependently reduced oxidative stresses, proinflammatory molecules, and well-preserved components of the neurovascular unit. The low-dose combination of
olmesartan plus
azelnidipine showed a better effect than the low-dose
olmesartan or
azelnidipine monotherapy. The present study shows that the low-dose combination of
olmesartan plus
azelnidipine demonstrates a greater synergistic benefit than monotherapy with a low-dose of
olmesartan or
azelnidipine in SHR-SP for preventing spontaneous
infarct volume, reducing oxidative stresses and proinflammatory molecules, and imparting neurovascular protection. In addition, a high-dose of
olmesartan showed a greater benefit without the lowering of blood pressure, probably because of the antioxidative and anti-inflammatory effects. A high dose of
azelnidipine showed the best benefit, probably because of the two effects mentioned above related to the lowering of blood pressure.