The sera of spontaneously hypertensive rats contain agonistic auto-antibodies against the ??1-radrenoceptor

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Abstract
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. Design: 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 β1-adrenergic receptor. Conclusions: The sera of the investigated ageing SHR contain agonistic auto-antibodies directed against the β1-adrenoceptor. These anti-β-adrenoceptor antibodies in the SHR, like those in the sera of cardiomyopathic patients, recognize in most cases the second extracellular loop of the β1-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 β1-adrenoceptor.

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