The sera of spontaneously hypertensive rats contain agonistic auto-antibodies against the beta 1-adrenoceptor.
OBJECTIVE
To examine auto-antibodies in the sera of spontaneously hypertensive rats (SHR) and investigate the possibility of abnormalities of the immune system in those rats.


METHODS
Blood samples were taken from 18-month-old SHR and age-matched Wistar-Kyoto (WKY) rats. The immunoglobulin fraction was prepared from the rat sera.


METHODS
Immunoglobulins were investigated in a sensitive biological test system using spontaneously beating neonatal rat heart myocytes.


RESULTS
Immunoglobulins prepared from the sera of the 18-month-old SHR increased the beating frequency of cultured rat heart myocytes. This positive chronotropic effect induced by the auto-antibody-containing immunoglobulin fraction was realized via the beta 1-adrenergic receptor.


CONCLUSIONS
The sera of the investigated ageing SHR contain agonistic auto-antibodies directed against the beta 1-adrenoceptor. These anti-beta-adrenoceptor antibodies in the SHR, like those in the sera of cardiomyopathic patients, recognize in most cases the second extracellular loop of the beta 1-adrenoceptor as the site of the antigenic determinant, and act in a similar way to the antibodies observed in the sera of cardiomyopathic patients. The present findings provide the opportunity of using ageing SHR as a model to investigate the development and possible pathogenic role of the agonistic auto-antibodies that recognize the beta 1-adrenoceptor.
Wallukat
G
G
Max Delbrück Centre for Molecular Medicine, Berlin, Germany.
Blasig
I E
IE
Morwinski
R
R
Herrmann
H J
HJ
Rohde
E
E
D000818:Animals; D001323:Autoantibodies / Q000097:blood*; D001794:Blood Pressure; D006332:Cardiomegaly / Q000503:physiopathology; D002478:Cells, Cultured; D006973:Hypertension / Q000276:immunology* / Q000503:physiopathology; D007136:Immunoglobulins / Q000494:pharmacology; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017208:Rats, Wistar; D018342:Receptors, Adrenergic, beta-1 / Q000187:drug effects / Q000276:immunology*
D001323:Autoantibodies; D007136:Immunoglobulins; D018342:Receptors, Adrenergic, beta-1