BACKGROUND: Current treatment for the secondary prevention of cardiovascular diseases frequently involves the prescription of several combination therapies, particularly antihypertensive medications and HMG-CoA reductase inhibitor. We have previously shown that in salt-sensitive hypertension either a statin or the calcium channel blocker amlodipine (Aml) have vasoprotective effects. Here, we investigated in aortas from Dahl salt-sensitive (DS) rats the effects of Aml, the statin atorvastatin (AT), and their combination on endothelial function, superoxide (O2 (-)) production, and the expression of endothelial nitric oxide synthase (eNOS), chemokine monocyte chemoattractant protein-1 (MCP-1), and lectin-like oxidized LDL receptor-1 (LOX-1). METHODS: Groups of DS rats were fed either normal-salt (NS, 0.5% NaCl) or high-salt (HS, 4% NaCl) diet or a HS diet with AT (15mg/kg/day), Aml (5mg/kg/day) or combination of AT/Aml for 6 weeks. RESULTS: Rats on the HS diet developed hypertension, aortic hypertrophy, accompanied by increased plasma C-reactive protein (CRP), aortic O2 (-), MCP-1 (80%), and LOX-1 (55%) expression and reduced eNOS and endothelial-dependent relaxation to acetylcholine (EDR). Aml reduced systolic blood pressure (SBP), aortic hypertrophy, plasma CRP, vascular O2 (-), and MCP-1 expression and improved eNOS and EDR. AT reduced aortic hypertrophy and plasma CRP, improved EDR, and normalized vascular O2 (-), eNOS, and proinflammatory gene expression with mild reduction in SBP. Combination therapy further reduced the SBP and normalized aortic hypertrophy, EDR, and plasma CRP. CONCLUSIONS: The combination therapy of Aml/AT has an additive beneficial effect on the vasculature. These novel findings may provide scientific basis for the combination therapy of statins with antihypertensive agents to reduce and prevent cardiovascular diseases.
BACKGROUND: Current treatment for the secondary prevention of cardiovascular diseases frequently involves the prescription of several combination therapies, particularly antihypertensive medications and HMG-CoA reductase inhibitor. We have previously shown that in salt-sensitive hypertension either a statin or the calcium channel blocker amlodipine (Aml) have vasoprotective effects. Here, we investigated in aortas from Dahl salt-sensitive (DS) rats the effects of Aml, the statin atorvastatin (AT), and their combination on endothelial function, superoxide (O2 (-)) production, and the expression of endothelial nitric oxide synthase (eNOS), chemokine monocyte chemoattractant protein-1 (MCP-1), and lectin-like oxidized LDL receptor-1 (LOX-1). METHODS: Groups of DS rats were fed either normal-salt (NS, 0.5% NaCl) or high-salt (HS, 4% NaCl) diet or a HS diet with AT (15mg/kg/day), Aml (5mg/kg/day) or combination of AT/Aml for 6 weeks. RESULTS:Rats on the HS diet developed hypertension, aortic hypertrophy, accompanied by increased plasma C-reactive protein (CRP), aortic O2 (-), MCP-1 (80%), and LOX-1 (55%) expression and reduced eNOS and endothelial-dependent relaxation to acetylcholine (EDR). Aml reduced systolic blood pressure (SBP), aortic hypertrophy, plasma CRP, vascular O2 (-), and MCP-1 expression and improved eNOS and EDR. AT reduced aortic hypertrophy and plasma CRP, improved EDR, and normalized vascular O2 (-), eNOS, and proinflammatory gene expression with mild reduction in SBP. Combination therapy further reduced the SBP and normalized aortic hypertrophy, EDR, and plasma CRP. CONCLUSIONS: The combination therapy of Aml/AT has an additive beneficial effect on the vasculature. These novel findings may provide scientific basis for the combination therapy of statins with antihypertensive agents to reduce and prevent cardiovascular diseases.