Arterial structural changes in rats immunized by AT1-receptor peptide

Accumulating evidence suggests that anti-AT(1) (angiotensin II receptor type 1) receptor antibodies are involved in the pathogenesis of hypertension. We assessed the hypothesis that changes in vascular structure could be induced in rats immunized with AT(1)-receptor peptide. In this study, an animal model was made by immunizing Wistar rats aged 4 weeks with the synthetic peptide corresponding to the second extracelluar peptide of human AT(1) as the antigen and raising them for 1 year, while monitoring their blood pressure, heart rate, and anti-AT(1)-receptor antibodies. A year later the aorta and mesenteric artery of the immunized rats were collected to detect their structural changes. Anti-AT(1)-receptor antibodies purified by affinity chromatography were prepared to detect their effect on vascular smooth muscle cell (VSMC) proliferation by the method of bromodeoxyuridine incorporation and cell cycle distribution, and their effect on the expression of VSMC c-jun and c-fos mRNA by reverse transcription-polymerase chain reaction and Western blot. Anti-AT(1)-receptor antibodies were detected in immunized rats throughout the year without significant changes in blood pressure or heart rate, but pathological changes in the arteries were noted at the end of the study period. Purified anti-AT(1)-receptor antibodies improved proliferation of VSMC and upregulated c-jun expression, which were both attenuated by losartan. In summary, anti-AT(1)-receptor antibodies can be prepared by active immunization with the peptide of AT(1) as the antigen, without changes in blood pressure or heart rate. Anti-AT(1)-receptor antibodies may play a role in hypertension through upregulation of c-jun expression, thus improving VSMC proliferation and finally inducing vascular recombination.