Combination therapy of amlodipine and atorvastatin has more beneficial vascular effects than monotherapy in salt-sensitive hypertension

Ming Sheng Zhou, Runxia Tian, Edgar A. Jaimes, Leopoldo Raij

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)873-880
Number of pages8
JournalAmerican Journal of Hypertension
Volume27
Issue number6
DOIs
StatePublished - Jan 1 2014

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Blood Vessels
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Salts
Nitric Oxide Synthase Type III
Blood Pressure
Hypertension
Amlodipine
C-Reactive Protein
Hypertrophy
Blood Proteins
Chemokine CCL2
Oxidized LDL Receptors
Inbred Dahl Rats
Diet
LDL Lipoproteins
Antihypertensive Agents
Cardiovascular Diseases
Therapeutics
Calcium Channel Blockers
Secondary Prevention

Keywords

  • amlodipine
  • blood pressure
  • combination ther apy
  • endothelial function
  • hypertension
  • statin

ASJC Scopus subject areas

  • Internal Medicine

Cite this

Combination therapy of amlodipine and atorvastatin has more beneficial vascular effects than monotherapy in salt-sensitive hypertension. / Zhou, Ming Sheng; Tian, Runxia; Jaimes, Edgar A.; Raij, Leopoldo.

In: American Journal of Hypertension, Vol. 27, No. 6, 01.01.2014, p. 873-880.

Research output: Contribution to journalArticle

Zhou, Ming Sheng ; Tian, Runxia ; Jaimes, Edgar A. ; Raij, Leopoldo. / Combination therapy of amlodipine and atorvastatin has more beneficial vascular effects than monotherapy in salt-sensitive hypertension. In: American Journal of Hypertension. 2014 ; Vol. 27, No. 6. pp. 873-880.
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abstract = "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.",
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T1 - Combination therapy of amlodipine and atorvastatin has more beneficial vascular effects than monotherapy in salt-sensitive hypertension

AU - Zhou, Ming Sheng

AU - Tian, Runxia

AU - Jaimes, Edgar A.

AU - Raij, Leopoldo

PY - 2014/1/1

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N2 - 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.

AB - 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.

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KW - hypertension

KW - statin

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