Agonist-like activity of antibodies to angiotensin II receptor subtype 1 (ATI) from rats immunized with AT1 receptor peptide

In the present study, rats were immunized with angiotensin II receptor subt ype 1 (AT1) receptor peptides for 3 months to see if the immunization produ ced specific anti-AT1 receptor antibodies and if continuous stimulation for 3 months affected blood pressure or induced morphological changes in the o rgans containing ATI receptors. Our results showed that there were constant high levels of circulating antibodies throughout the study period in all r ats of the immunized group, but not in the control rats, and that there wer e almost no significant cross-reactions of antisera with AT2 receptor pepti de and alpha 1 adrenoceptor peptide, except in four rats, which showed low cross-reactions with alpha 1 adrenoceptor and AT2 receptor peptides. When a n affinity-purified anti-AT1 receptor antibody was used, it specifically di splayed the AT1-stimulatory positive chronotropic effect and also localized AT1 receptors. However, in the immunized group, saturation binding of AT1 in homogenates from kidneys showed no difference either in maximal binding sites (Bmax) or in antagonist affinity (Kd). No difference in mRNA of AT1a was found in either kidney or heart, and no morphological changes in the or gans were observed, as compared with the control group. Furthermore, immuni zation did not cause hypertension. In conclusion, the synthetic peptide cor responding to the second extra-cellular loop of the human AT1 receptor was able to produce highly specific and functionally active anti-AT1 receptor a ntibodies, but unable to induce pathological structural changes or hyperten sion.