Norepinephrine-induced cardiac hypertrophy and fibrosis are not due to mast cell degranulation.
The norepinephrine (NE)-induced hypertrophy of the left ventricle (LV) in the rat is preceded by increased interleukin (IL)-6 expression and associated with LV fibrosis. We have examined whether the elevated level of IL-6 may be due to mast cell degranulation. Therefore we tested the effect of cromoglycate sodium salt (cromolyn), an inhibitor of mast cell degranulation with anti-inflammatory and membrane-stabilizing activity, on the increased expression of IL-6 mRNA and of mRNAs of proteins involved in the remodelling of the extracellular matrix (ECM) which is induced by NE (0.1 mg/kg x h). After 4 h, the NE-induced increase in IL-6 mRNA expression was not influenced by cromolyn (20 mg/kg x h). Cromolyn-infusion for 3 days did not affect the extent of LV hypertrophy induced by NE, as measured by the LV weight/body weight (LVW/BW) ratio and by atrial natriuretic peptide (ANP) expression. Cromolyn induced a slight depression of the NE-induced elevation of the matrix metalloproteinase (MMP)-2. However, it did not affect the NE-induced elevated levels of mRNAs of collagen I and III and the tissue inhibitor of matrix metalloproteinase (TIMP)-2. Since cromolyn did not reduce the NE-effects in rat hearts in vivo we conclude that mast cell degranulation seems not to be involved in them.
Briest
Wilfried
W
Carl-Ludwig-Institute of Physiology, University of Leipzig, Leipzig, Germany. briestw@medizin.uni-leipzig.de
Rassler
Beate
B
Deten
Alexander
A
Zimmer
Heinz-Gerd
HG
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000235:genetics; D006332:Cardiomegaly / Q000139:chemically induced*; D015550:Cell Degranulation; D005260:Female; D005355:Fibrosis / Q000139:chemically induced*; D006439:Hemodynamics; D015850:Interleukin-6 / Q000235:genetics; D008407:Mast Cells / Q000473:pathology*; D009638:Norepinephrine / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley
D015850:Interleukin-6; D012333:RNA, Messenger; D009320:Atrial Natriuretic Factor; D009638:Norepinephrine