Key result
The combination of the calcium channel blocker azelnidipine and the ARB olmesartan significantly enhanced protection against cognitive decline, blood-brain barrier disruption, and renal injury compared to olmesartan alone in type 2 diabetic mice.
Why the study?
Does the combination of azelnidipine and olmesartan improve cerebrovascular-renal injury in type 2 diabetic mice compared to olmesartan alone?
Does the combination of azelnidipine and olmesartan improve cerebrovascular-renal injury in type 2 diabetic mice compared to olmesartan alone?
p-value: p=<0.05
In a type 2 diabetic mouse model, the addition of a calcium channel blocker to an ARB synergistically protected against cerebrovascular and renal injury by suppressing oxidative stress.
Recent clinical trials have demonstrated that combination therapy with renin-angiotensin system inhibitors plus calcium channel blockers (CCBs) elicits beneficial effects on cardiovascular and renal events in hypertensive patients with high cardiovascular risks. In the present study, we hypothesized that CCB enhances the protective effects of an angiotensin II type 1 receptor blocker (ARB) against diabetic cerebrovascular-renal injury. Saline-drinking type 2 diabetic KK-A(y) mice developed hypertension and exhibited impaired cognitive function, blood-brain barrier (BBB) disruption, albuminuria, glomerular sclerosis and podocyte injury. These brain and renal injuries were associated with increased gene expression of NADPH oxidase components, NADPH oxidase activity and oxidative stress in brain and kidney tissues as well as systemic oxidative stress. Treatment with the ARB, olmesartan (10 mg/kg/day) reduced blood pressure in saline-drinking KK-A(y) mice and attenuated cognitive decline, BBB disruption, glomerular injury and albuminuria, which were associated with a reduction of NADPH oxidase activity and oxidative stress in brain and kidney tissues as well as systemic oxidative stress. Furthermore, a suppressive dose of azelnidipine (3 mg/kg/day) exaggerated these beneficial effects of olmesartan. These data support the hypothesis that a CCB enhances ARB-associated cerebrovascular-renal protective effects through suppression of NADPH oxidase-dependent oxidative stress in type 2 diabetes.
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Rafiq et al. (2013) studied Type 2 diabetes with cerebrovascular-renal injury (n=66). Olmesartan plus azelnidipine vs. Olmesartan alone or saline-drinking disease control was evaluated on Cerebrovascular-renal injury (cognitive decline, BBB disruption, albuminuria, glomerular sclerosis) (p=<0.05). The combination of the calcium channel blocker azelnidipine and the ARB olmesartan significantly enhanced protection against cognitive decline, blood-brain barrier disruption, and renal injury compared to olmesartan alone in type 2 diabetic mice.
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