Linked Life Data

1697370

Source:http://linkedlifedata.com/resource/pubmed/id/1697370

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PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
1990-10-4
pubmed:abstractText
Local inhibition of angiotensin-converting enzyme (ACE, kininase II) produces both attenuation of angiotensin (Ang) II generation and bradykinin (BK) degradation. To delineate the participation of BK in the cardioprotective actions of ACE inhibitors, experiments were performed in rats and dogs with cardiac ischemia-reperfusion injuries. (I) In rat isolated perfused working hearts with regional myocardial ischemia, BK in concentrations as low as 1 X 10(-9) M increased coronary flow (CF) and reduced the incidence and duration of reperfusion ventricular fibrillation (VF). In addition, enzyme activities of lactate dehydrogenase (LDH) and creatine kinase as well as lactate output were decreased in the venous effluent of BK-perfused hearts, which also showed improved cardiodynamic and metabolic parameters. Even concentrations of BK lower than 1 X 10(-10) M, which were without influence on coronary flow, exerted comparable beneficial metabolic effects connected with reduced incidence and duration of VF. Combined perfusions with threshold concentrations of BK (1 X 10(-12) M) and the ACE inhibitor ramiprilat (2.58 X 10(-9) M), which were ineffective given alone, resulted in a marked cardioprotective effect. Perfusion with Ang II (1 X 10(-9) M) aggravated reperfusion arrhythmias and worsened myocardial metabolism. BK perfusion prevented this deterioration in a concentration-dependent manner, whereas the Ang II receptor antagonist saralasin was only marginally effective. The BK antagonist D-Arg-[Hyp2, Thi5,8, D-Phe7]-BK (1 X 10(-5) M) completely abolished the cardioprotective effects of BK or the ACE inhibitor. However, higher concentrations of BK (1 X 10(-7) M) or ramiprilat (2.58 X 10(-5) M) competitively reversed these properties of the BK antagonist. (II) In anesthetized dogs, BK was infused into the coronary artery in a dose of 1 ng/kg/min during occlusion (90 min) and reperfusion (30 min) of the left descending coronary artery (LAD)--a dose without effects on cardiovascular parameters. In line with the findings in isolated ischemic rat hearts, BK infusion reduced LDH activities and lactate concentrations in the coronary sinus blood, whereas myocardial tissue levels of glycogen and energy-rich phosphates were increased in the infarcted area. The cardioprotective effects produced by perfusion with BK or by reduction of BK degradation through local interference with ACE favor a role for BK in ischemia-reperfusion injuries in rats and dogs.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0160-2446
pubmed:author
pubmed:issnType
Print
pubmed:volume
15 Suppl 6
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
S99-109
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:1697370-Anesthesia, pubmed-meshheading:1697370-Angiotensin-Converting Enzyme Inhibitors, pubmed-meshheading:1697370-Animals, pubmed-meshheading:1697370-Arrhythmias, Cardiac, pubmed-meshheading:1697370-Bradykinin, pubmed-meshheading:1697370-Coronary Circulation, pubmed-meshheading:1697370-Coronary Disease, pubmed-meshheading:1697370-Dogs, pubmed-meshheading:1697370-Female, pubmed-meshheading:1697370-Hemodynamics, pubmed-meshheading:1697370-L-Lactate Dehydrogenase, pubmed-meshheading:1697370-Lactates, pubmed-meshheading:1697370-Male, pubmed-meshheading:1697370-Myocardial Reperfusion Injury, pubmed-meshheading:1697370-Myocardium, pubmed-meshheading:1697370-Pyrroles, pubmed-meshheading:1697370-Ramipril, pubmed-meshheading:1697370-Rats, pubmed-meshheading:1697370-Rats, Inbred Strains, pubmed-meshheading:1697370-Saralasin
pubmed:year
1990
pubmed:articleTitle
Local inhibition of bradykinin degradation in ischemic hearts.
pubmed:affiliation
Hoechst AG, Frankfurt, F.R.G.
pubmed:publicationType
Journal Article, In Vitro