G. Wallukat et al., THE SERA OF SPONTANEOUSLY HYPERTENSIVE RATS CONTAIN AGONISTIC AUTOANTIBODIES AGAINST THE BETA(1)-ADRENOCEPTOR, Journal of hypertension, 13(9), 1995, pp. 1031-1036
Objective: To examine auto-antibodies in the sera of spontaneously hyp
ertensive rats (SHR) and investigate the possibility of abnormalities
of the immune system in those rats. Design: Blood samples were taken f
rom 18-month-old SHR and age-matched Wistar-Kyoto (WKY) rats. The immu
noglobulin fraction was prepared from the rat sera. Methods: Immunoglo
bulins were investigated in a sensitive biological test system using s
pontaneously beating neonatal rat heart myocytes. Results: Immunoglobu
lins prepared from the sera of the 18-month-old SHR increased the beat
ing frequency of cultured rat heart myocytes. This positive chronotrop
ic effect induced by the auto-antibody-containing immunoglobulin fract
ion 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(1)-adrenoc
eptor antibodies in the SHR, like those in the sera of cardiomyopathic
patients, recognize in most cases the second extracellular loop of th
e beta(1)-adrenoceptor as the site of the antigenic determinant, and a
ct in a similar way to the antibodies observed in the sera of cardiomy
opathic patients. The present findings provide the opportunity of usin
g ageing SHR as a model to investigate the development and possible pa
thogenic role of the agonistic auto-antibodies that recognize the beta
(1)-adrenoceptor.