PMID- 24413709
OWN - NLM
STAT- MEDLINE
DCOM- 20141229
LR  - 20211021
IS  - 1941-7225 (Electronic)
IS  - 0895-7061 (Linking)
VI  - 27
IP  - 6
DP  - 2014 Jun
TI  - Combination therapy of amlodipine and atorvastatin has more beneficial vascular 
      effects than monotherapy in salt-sensitive hypertension.
PG  - 873-80
LID - 10.1093/ajh/hpt272 [doi]
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.
FAU - Zhou, Ming-Sheng
AU  - Zhou MS
AD  - Department of Physiology, Liaoning Medical University, Jinzhou, P.R. of China.
FAU - Tian, Runxia
AU  - Tian R
FAU - Jaimes, Edgar A
AU  - Jaimes EA
FAU - Raij, Leopoldo
AU  - Raij L
LA  - eng
GR  - I01 BX001073/BX/BLRD VA/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20140111
PL  - United States
TA  - Am J Hypertens
JT  - American journal of hypertension
JID - 8803676
RN  - 0 (Antihypertensive Agents)
RN  - 0 (Calcium Channel Blockers)
RN  - 0 (Ccl2 protein, rat)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Heptanoic Acids)
RN  - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors)
RN  - 0 (OLR1 protein, rat)
RN  - 0 (Pyrroles)
RN  - 0 (Scavenger Receptors, Class E)
RN  - 0 (Sodium Chloride, Dietary)
RN  - 11062-77-4 (Superoxides)
RN  - 1J444QC288 (Amlodipine)
RN  - 9007-41-4 (C-Reactive Protein)
RN  - A0JWA85V8F (Atorvastatin)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type III)
RN  - EC 1.14.13.39 (Nos3 protein, rat)
SB  - IM
MH  - Amlodipine/*pharmacology
MH  - Animals
MH  - Antihypertensive Agents/*pharmacology
MH  - Aorta/*drug effects/metabolism/pathology/physiopathology
MH  - Atorvastatin
MH  - Blood Pressure/drug effects
MH  - C-Reactive Protein/metabolism
MH  - Calcium Channel Blockers/*pharmacology
MH  - Chemokine CCL2/metabolism
MH  - Disease Models, Animal
MH  - Drug Therapy, Combination
MH  - Heptanoic Acids/*pharmacology
MH  - Hydroxymethylglutaryl-CoA Reductase Inhibitors/*pharmacology
MH  - Hypertension/*drug therapy/etiology/metabolism/pathology/physiopathology
MH  - Hypertrophy
MH  - Male
MH  - Nitric Oxide Synthase Type III/metabolism
MH  - Pyrroles/*pharmacology
MH  - Rats, Inbred Dahl
MH  - Scavenger Receptors, Class E/metabolism
MH  - *Sodium Chloride, Dietary
MH  - Superoxides/metabolism
MH  - Time Factors
MH  - Vasodilation/drug effects
OTO - NOTNLM
OT  - amlodipine
OT  - blood pressure
OT  - combination therapy
OT  - endothelial function
OT  - hypertension
OT  - statin
EDAT- 2014/01/15 06:00
MHDA- 2014/12/30 06:00
CRDT- 2014/01/14 06:00
PHST- 2014/01/14 06:00 [entrez]
PHST- 2014/01/15 06:00 [pubmed]
PHST- 2014/12/30 06:00 [medline]
AID - hpt272 [pii]
AID - 10.1093/ajh/hpt272 [doi]
PST - ppublish
SO  - Am J Hypertens. 2014 Jun;27(6):873-80. doi: 10.1093/ajh/hpt272. Epub 2014 Jan 11.