Effect of propranolol on cardiac cytokine expression after myocardial infarction in rats.
The pro-inflammatory cytokines interleukin (IL)-1beta and IL-6 have been shown to be upregulated in the myocardium after injury and after adrenergic receptor stimulation. Together with other cytokines, such as the transforming growth factor (TGF)-beta, the pro-inflammatory cytokines have been implicated in the initiation of tissue repair and wound healing after myocardial infarction (MI). In the present study, the effect of beta-adrenergic receptor blockade with propranolol (2 mg/kg x h s.c. by miniosmotic pumps) on cardiac cytokine expression and on wound healing was analyzed in rats from 6-72 h after MI. IL-1beta and IL-6 gene expression strongly increased in the infarcted myocardium 6 h after MI and peaked after 12 h, while TGF-beta, progressively increased from 12 h onwards. Also, TGF-beta2 increased after 12 h, peaked after 24 h and declined thereafter, while TGF-beta, was only elevated after 72 h. Treatment with propranolol had a negative chronotropic effect throughout the observation period of 72 h. It attenuated the initial elevation in LVEDP and increased cardiac output ultimately. Furthermore, propranolol attenuated IL-1beta mRNA expression, but had not effect on the other cytokines. Moreover, MMP-9 gelatinolytic activity was markedly attenuated by propranolol indicating a delayed resorption of the necrotic tissue and, possibly, collagen turnover. Replacement by scar tissue, however, was not affected as indicated by normal collagen expression.
Carl-Ludwig-Institute of Physiology, University of Leipzig, Leipzig, Germany. deta@medizin.uni-leipzig.de
Alexander
A
Deten
Hans Christian
HC
Volz
Alexander
A
Holzl
Wilfried
W
Briest
Heinz-Gerd
HG
Zimmer
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003094:Collagen / Q000187:drug effects / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D020780:Matrix Metalloproteinase 9 / Q000187:drug effects / Q000378:metabolism; D009203:Myocardial Infarction / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism; D009336:Necrosis; D011433:Propranolol / Q000494:pharmacology*; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors; D015854:Up-Regulation; D017725:Ventricular Pressure / Q000187:drug effects; D014945:Wound Healing / Q000187:drug effects
D000319:Adrenergic beta-Antagonists; D016207:Cytokines; D012333:RNA, Messenger; D011943:Receptors, Adrenergic, beta; D003094:Collagen; D011433:Propranolol; D020780:Matrix Metalloproteinase 9