| Wortmannin, a potent antineutrophil agent, exerts cardioprotective effects in myocardial ischemia/reperfusion. | |
| | |
MedLine Citation:
|
PMID: 10991958 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Ischemia followed by reperfusion in the presence of polymorphonuclear leukocytes (PMNs) results in a marked cardiac contractile dysfunction. Wortmannin, a specific inhibitor of phosphatidylinositol 3-kinase, suppresses superoxide production from PMNs. Therefore, we hypothesized that wortmannin could attenuate PMN-induced cardiac dysfunction by suppression of superoxide production from PMNs. We examined the effects of wortmannin in isolated ischemic (20 min) and reperfused (45 min) rat hearts perfused with PMNs. Wortmannin at 10, 20, or 40 nM given to hearts during the first 5 min of reperfusion, significantly improved left ventricular developed pressure (P < .01), and the maximal rate of development of left ventricular developed pressure (P < .01) compared with ischemic/reperfused hearts perfused with PMNs in the absence of wortmannin. In addition, wortmannin significantly reduced PMN infiltration into the myocardium by 50 to 75% (P < .001). Superoxide radical release also was significantly reduced in N-formylmethionyl-leucylphenylalanine-stimulated PMNs pretreated with 10 or 40 nM wortmannin by 70 and 95%, respectively (P < .001 versus untreated PMNs). Rat PMN adherence to rat superior mesenteric artery endothelium exposed to 2 U/ml thrombin was significantly attenuated by 10 to 40 nM wortmannin compared with untreated vessels (P < .001). These results provide evidence that wortmannin can significantly attenuate PMN-induced cardiac contractile dysfunction in the ischemic/reperfused rat heart via attenuation of PMN infiltration into the myocardium and suppression of superoxide release by PMNs. |
| | |
Authors:
|
L H Young; Y Ikeda; R Scalia; A M Lefer |
Related Documents
:
|
23361078 - Connexin43 and angiotensin ii alterations in hearts of rats having undergone an acute e... 8678778 - Effect of hyperbaric oxygen on neutrophil concentration and pulmonary sequestration in ... 1521558 - Cardioprotective effect of pindolol in ischemic-reperfused isolated rat hearts. 9366438 - Lipocortin 1 protects against splanchnic artery occlusion and reperfusion injury by aff... 7498418 - Neonatal isolation enhances hippocampal dentate response to tetanization in freely movi... 23270878 - Anticonvulsant, neuroprotective and behavioral effects of organic and conventional yerb... |
Publication Detail:
|
Type: Journal Article; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
|
Title: The Journal of pharmacology and experimental therapeutics Volume: 295 ISSN: 0022-3565 ISO Abbreviation: J. Pharmacol. Exp. Ther. Publication Date: 2000 Oct |
Date Detail:
|
Created Date: 2000-11-03 Completed Date: 2000-11-03 Revised Date: 2007-11-15 |
Medline Journal Info:
|
Nlm Unique ID: 0376362 Medline TA: J Pharmacol Exp Ther Country: UNITED STATES |
Other Details:
|
Languages: eng Pagination: 37-43 Citation Subset: IM |
Affiliation:
|
Department of Physiology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
1-Phosphatidylinositol 3-Kinase
/
physiology Androstadienes / pharmacology* Animals Heart / drug effects* Male Myocardial Ischemia / drug therapy* Myocardial Reperfusion Injury / prevention & control* Neutrophils / drug effects* Rats Rats, Sprague-Dawley Type C Phospholipases / physiology |
| Grant Support | |
ID/Acronym/Agency:
|
GM-45434/GM/NIGMS NIH HHS; HL-07599/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/Androstadienes; 19545-26-7/wortmannin; EC 2.7.1.137/1-Phosphatidylinositol 3-Kinase; EC 3.1.4.-/Type C Phospholipases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Inhibition of volume-regulated and calcium-activated chloride channels by the antimalarial mefloquin...
Next Document: Hepatic disposition of the acyl glucuronide 1-O-gemfibrozil-beta-D-glucuronide: effects of clofibric...