Document Detail


Effects of selective cyclooxygenase-2 and nonselective cyclooxygenase inhibition on myocardial function and perfusion.
MedLine Citation:
PMID:  21233641     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Nonselective nonsteroidal anti-inflammatory drugs and selective cyclooxygenase-2 (COX-2) inhibitors are purported to increase adverse cardiovascular events. We hypothesized that COX-2 inhibitors would alter myocardial blood flow, microvascular reactivity, oxidative stress, and prostaglandin levels. Adult Yorkshire swine were divided into 3 groups: no drug (control, n = 7), a nonselective COX inhibitor (naproxen 400 mg daily, NAP, n = 7), or a selective COX-2 inhibitor (celecoxib 200 mg daily, CBX, n = 7). After 7 weeks, physiologic measurements were taken and tissue harvested. Animals in the CBX group demonstrated significantly higher blood pressure and rate-pressure product. The NAP and CBX groups demonstrated an increased microvascular contraction response to serotonin. The NAP group showed increased myocardial levels of thromboxane and lower levels of prostacyclin. Levels of protein oxidative stress were increased in the CBX group. Myocardial apoptosis was lowest in the NAP group. Immunoblotting demonstrated decreased vascular endothelial growth factor and phosphorylated endothelial nitric oxide synthase expression in the NAP and CBX groups. Myocardial tumor necrosis factor-α was increased in both treated groups. Immunostaining for thromboxane A2 synthase and receptor demonstrated expression within the vascular smooth muscle and no observable differences between groups. Nonselective and selective COX inhibition does not alter myocardial perfusion but results in altered myocardial and vascular physiology that may have implications regarding cardiovascular risk.
Authors:
Michael P Robich; Louis M Chu; Thomas A Burgess; Jun Feng; Cesario Bianchi; Frank W Sellke
Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of cardiovascular pharmacology     Volume:  57     ISSN:  1533-4023     ISO Abbreviation:  J. Cardiovasc. Pharmacol.     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2011-01-14     Completed Date:  2011-06-01     Revised Date:  2014-09-19    
Medline Journal Info:
Nlm Unique ID:  7902492     Medline TA:  J Cardiovasc Pharmacol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  122-30     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Anti-Inflammatory Agents, Non-Steroidal / adverse effects,  metabolism,  therapeutic use
Cyclooxygenase 2 / metabolism*
Cyclooxygenase Inhibitors / adverse effects,  pharmacology*,  therapeutic use
Epoprostenol / metabolism
Muscle, Smooth, Vascular / metabolism
Myocardium / metabolism*
Nitric Oxide Synthase Type III / metabolism
Perfusion / methods
Risk
Swine
Swine, Miniature
Thromboxanes / metabolism
Tumor Necrosis Factor-alpha / metabolism
Grant Support
ID/Acronym/Agency:
5T32-HL0074/HL/NHLBI NIH HHS; R01 HL046716/HL/NHLBI NIH HHS; R01 HL046716-18A1/HL/NHLBI NIH HHS; R01 HL069024/HL/NHLBI NIH HHS; R01 HL069024-09/HL/NHLBI NIH HHS; R01 HL085647/HL/NHLBI NIH HHS; R01 HL085647-03/HL/NHLBI NIH HHS; R01HL46716/HL/NHLBI NIH HHS; R01HL69024/HL/NHLBI NIH HHS; R01HL85647/HL/NHLBI NIH HHS; T32 HL076130/HL/NHLBI NIH HHS; T32 HL076130-05/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Anti-Inflammatory Agents, Non-Steroidal; 0/Cyclooxygenase Inhibitors; 0/Thromboxanes; 0/Tumor Necrosis Factor-alpha; DCR9Z582X0/Epoprostenol; EC 1.14.13.39/Nitric Oxide Synthase Type III; EC 1.14.99.1/Cyclooxygenase 2
Comments/Corrections

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