Protein Kinase C βII Peptide Inhibitor Exerts Cardioprotective Effects in Rat Cardiac Ischemia/Reperfusion Injury
| Autor: | Norrell Atkinson, Richard J. Brue, Didi Omiyi, Philip Taormina, Lindon H. Young, Margaret Harvey |
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| Rok vydání: | 2005 |
| Předmět: |
Male
Cardiac function curve medicine.medical_specialty Cardiotonic Agents Nitric Oxide Synthase Type III Neutrophils Ischemia Aorta Thoracic Blood Pressure Myocardial Reperfusion Injury Receptors Cell Surface Protein Kinase C beta In Vitro Techniques Nitric Oxide Receptors for Activated C Kinase Ventricular Function Left Nitric oxide Rats Sprague-Dawley chemistry.chemical_compound Superoxides Internal medicine Cell Adhesion medicine Animals Pyrroles Enzyme Inhibitors Protein Kinase C Protein kinase C Mesylates Pharmacology biology Chemistry Superoxide Myocardium medicine.disease Myocardial Contraction Rats Isoenzymes Nitric oxide synthase NG-Nitroarginine Methyl Ester Endocrinology biology.protein Molecular Medicine Nitric Oxide Synthase Reperfusion injury |
| Zdroj: | Journal of Pharmacology and Experimental Therapeutics. 314:542-551 |
| ISSN: | 1521-0103 0022-3565 |
| DOI: | 10.1124/jpet.104.082131 |
| Popis: | Ischemia followed by reperfusion (I/R) in the presence of polymorphonuclear leukocytes (PMNs) results in a marked cardiac contractile dysfunction. A cell-permeable protein kinase C (PKC) betaII peptide inhibitor was used to test the hypothesis that PKC betaII inhibition could attenuate PMN-induced cardiac dysfunction by suppression of superoxide production from PMNs and increase NO release from vascular endothelium. The effects of the PKC betaII peptide inhibitor were examined in isolated ischemic (20 min) and reperfused (45 min) rat hearts with PMNs. The PKC betaII inhibitor (10 microM; n = 7) significantly attenuated PMN-induced cardiac dysfunction compared with I/R hearts (n = 9) receiving PMNs alone in left ventricular developed pressure (LVDP) and the maximal rate of LVDP (+dP/dt(max)) cardiac function indices (p < 0.01). The PKC betaII inhibitor at 10 microM significantly increased endothelial NO release from a basal value of 1.85 +/- 0.18 pmol NO/mg tissue to 3.49 +/- 0.62 pmol NO/mg tissue from rat aorta. It also significantly inhibited superoxide release (i.e., absorbance) from N-formyl-L-methionyl-L-leucyl-L-phenylalanine-stimulated rat PMNs from 0.13 +/- 0.01 to 0.02 +/- 0.004 (p < 0.01) at 10 microM. Histological analysis of the left ventricle of representative rat hearts from each group showed that the PKC betaII peptide inhibitor-treated hearts experienced a marked reduction in PMN vascular adherence and infiltration into the postreperfused cardiac tissue compared with I/R + PMN hearts (p < 0.01). These results suggest that the PKC betaII peptide inhibitor attenuates PMN-induced post-I/R cardiac contractile dysfunction by increasing endothelial NO release and by inhibiting superoxide release from PMNs. |
| Databáze: | OpenAIRE |
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