Source:http://linkedlifedata.com/resource/pubmed/id/10750596
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
12A
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| pubmed:dateCreated |
2000-4-19
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| pubmed:abstractText |
The production of endogenous nitric oxide, which regulates myocardial oxygen consumption, is decreased in heart failure. As with angiotensin-converting enzyme (ACE) inhibitors, amlodipine, a calcium antagonist, increases kinin-mediated nitric oxide production in coronary microvessels. We investigated the possibility of synergy between ACE inhibitors and amlodipine in regulating myocardial oxygen consumption. Left ventricular myocardium was isolated from 6 healthy dog hearts and 5 human hearts with end-stage heart failure at the time of orthotopic heart transplantation. Myocardial oxygen consumption was measured before and after administration of bradykinin, S-nitroso N-acetyl penicillamine (SNAP, a nitric oxide donor), ramiprilat (an ACE inhibitor), amlodipine, and the combination of a sub-threshold dose of ramiprilat (10(-8) md/L) + amlodipine. These experiments were repeated with L-nitro-arginine methyl ester (L-NAME, an inhibitor of nitric oxide synthesis), dichloroisocoumarin (an inhibitor of kinin synthesis), and HOE 140 (a B2 kinin-receptor antagonist). Baseline myocardial oxygen consumption in canine hearts was 182 +/- 21 nmol/g/min. Bradykinin and SNAP caused dose-dependent reductions in myocardial oxygen consumption (p <0.05). Ramiprilat and amlodipine caused a 10 +/- 3.2% and 11 +/- 0.8% reduction in myocardial oxygen consumption, respectively, when used alone (p <0.05). In the presence of a subthreshold dose of ramiprilat, amlodipine caused a larger (15 +/- 1.7%) reduction in myocardial oxygen consumption compared with either drug used alone (p <0.05). In human hearts, baseline myocardial oxygen consumption was 248 +/- 57 nmol/g/min. Amlodipine caused a larger reduction in myocardial oxygen consumption when used with ramiprilat (22 +/- 3.2%) as compared with amlodipine alone (15 +/- 2.6%). The effect of both drugs was attenuated by L-NAME, dichloroisocoumarin, and HOE 140 (p <0.05). In conclusion, ACE inhibitors and amlodipine act synergistically to regulate myocardial oxygen consumption by modulating kinin-mediated nitric oxide release, and this combination of drugs may be useful in the treatment of heart failure.
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| pubmed:grant | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
AIM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/3,4-dichloroisocoumarin,
http://linkedlifedata.com/resource/pubmed/chemical/Adrenergic beta-Antagonists,
http://linkedlifedata.com/resource/pubmed/chemical/Amlodipine,
http://linkedlifedata.com/resource/pubmed/chemical/Angiotensin-Converting Enzyme...,
http://linkedlifedata.com/resource/pubmed/chemical/Bradykinin,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium Channel Blockers,
http://linkedlifedata.com/resource/pubmed/chemical/Coumarins,
http://linkedlifedata.com/resource/pubmed/chemical/NG-Nitroarginine Methyl Ester,
http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide Synthase,
http://linkedlifedata.com/resource/pubmed/chemical/Penicillamine,
http://linkedlifedata.com/resource/pubmed/chemical/Ramipril,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Bradykinin,
http://linkedlifedata.com/resource/pubmed/chemical/S-nitro-N-acetylpenicillamine,
http://linkedlifedata.com/resource/pubmed/chemical/Serine Proteinase Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/icatibant,
http://linkedlifedata.com/resource/pubmed/chemical/ramiprilat
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| pubmed:status |
MEDLINE
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| pubmed:month |
Jun
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| pubmed:issn |
0002-9149
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:day |
17
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| pubmed:volume |
83
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
92H-98H
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| pubmed:dateRevised |
2007-11-15
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| pubmed:meshHeading |
pubmed-meshheading:10750596-Adolescent,
pubmed-meshheading:10750596-Adrenergic beta-Antagonists,
pubmed-meshheading:10750596-Adult,
pubmed-meshheading:10750596-Amlodipine,
pubmed-meshheading:10750596-Angiotensin-Converting Enzyme Inhibitors,
pubmed-meshheading:10750596-Animals,
pubmed-meshheading:10750596-Bradykinin,
pubmed-meshheading:10750596-Calcium Channel Blockers,
pubmed-meshheading:10750596-Child,
pubmed-meshheading:10750596-Coumarins,
pubmed-meshheading:10750596-Dogs,
pubmed-meshheading:10750596-Drug Synergism,
pubmed-meshheading:10750596-Drug Therapy, Combination,
pubmed-meshheading:10750596-Female,
pubmed-meshheading:10750596-Heart Failure,
pubmed-meshheading:10750596-Humans,
pubmed-meshheading:10750596-Male,
pubmed-meshheading:10750596-Middle Aged,
pubmed-meshheading:10750596-Myocardial Contraction,
pubmed-meshheading:10750596-Myocardium,
pubmed-meshheading:10750596-NG-Nitroarginine Methyl Ester,
pubmed-meshheading:10750596-Nitric Oxide Synthase,
pubmed-meshheading:10750596-Oxygen Consumption,
pubmed-meshheading:10750596-Penicillamine,
pubmed-meshheading:10750596-Ramipril,
pubmed-meshheading:10750596-Receptors, Bradykinin,
pubmed-meshheading:10750596-Serine Proteinase Inhibitors
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| pubmed:year |
1999
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| pubmed:articleTitle |
Synergy of amlodipine and angiotensin-converting enzyme inhibitors in regulating myocardial oxygen consumption in normal canine and failing human hearts.
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| pubmed:affiliation |
Columbia University College of Physicians and Surgeons, New York, New York, USA.
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| pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, U.S. Gov't, P.H.S.
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