Detection of mRNA encoding H(1) receptor and iNOS by RT-PCR in autoimmune myocarditis with special reference to changes in heart contractility.
Cardiac tissue from autoimmune myocarditis mice was studied to evaluate the expression and biological activity of mRNA encoding H(1) receptor and iNOS. BALB/c inbred mice were immunized with heart protein and sacrificed at 20, 45 and 50 days post immunization. Heart contractility studies and RT-PCR assays were performed. Heart from autoimmune myocarditis mice show mRNA iNOS-related dysfunction with a decrease in heart contractility. This effect was accompanied with an increase production of cyclic GMP and was improved by treating autoimmune mice with an inhibitor of iNOS activity. In addition, autoimmune myocardium expressed an active histamine H(1) receptor mRNA coupled to phospholipase C. The activation of H(1) receptor by ThEA stimulated both phosphoinositide hydrolysis and heart contractility. Normal myocardium did not expressed neither iNOS mRNA nor H(1) receptor mRNA. In conclusions: the development of autoimmune cardiac dysfunction was associated with the expression of iNOS mRNA, cyclic GMP accumulation and the expression of an active histamine H(1) receptor mRNA with increase production of inositol phosphates. These protein emergence during the course of autoimmune myocarditis may be involved a distinct compensatory mechanism operating in this disease.
Goren
N
N
Pharmacologic Unit, School of Dentistry, University of Buenos Aires, Marcelo T. de Alvear 2142, 4 to Floor Sector B, 1122, Buenos Aires, Argentina.
Sterin-Borda
L
L
Bartrons
R
R
Gomez
R
R
Borda
E
E
D000818:Animals; D006152:Cyclic GMP / Q000378:metabolism; D007295:Inositol Phosphates / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009200:Myocardial Contraction / Q000276:immunology; D009205:Myocarditis / Q000201:enzymology / Q000276:immunology / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D011863:Radioimmunoassay; D011969:Receptors, Histamine H1 / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D007295:Inositol Phosphates; D012333:RNA, Messenger; D011969:Receptors, Histamine H1; D019001:Nitric Oxide Synthase; D006152:Cyclic GMP