Active immunization with angiotensin I peptide analogue vaccines selectively reduces the pressor effects of exogenous angiotensin I in conscious rats

• Published in: British journal of pharmacology Vol. 129; no. 6; pp. 1178 - 1182
• Main Authors: Gardiner, S M, Auton, T R, Downham, M R, Sharp, H L, Kemp, P A, March, J E, Martin, H, Morgan, P J, Rushton, A, Bennett, T, Glover, J F
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.03.2000; Nature Publishing
• Subjects: Algorithms; Angiotensin I - analogs & derivatives; Angiotensin I - immunology; Angiotensin I - pharmacology; Angiotensin II - analogs & derivatives; Angiotensin II - immunology; Angiotensin II - pharmacology; Angiotensin vaccines; angiotensinogen; Angiotensinogen - immunology; Angiotensinogen - pharmacology; Animals; Antibodies, Blocking - analysis; Antibodies, Blocking - immunology; antibody titres; Biological and medical sciences; Blood Pressure - drug effects; Blood Pressure - immunology; Blotting, Western; Carrier Proteins - immunology; Cross Reactions; Electrophoresis, Polyacrylamide Gel; Enzyme-Linked Immunosorbent Assay; Immunomodulators; Male; Medical sciences; Pharmacology. Drug treatments; pressor responses; Rats; Rats, Sprague-Dawley; Serine Proteinase Inhibitors - pharmacology; Vaccines - immunology; Vasoconstrictor Agents - pharmacology; Immunization; Immune response; Rat; Enzyme; Angiotensin I; Antibody; Rodentia; Metalloendopeptidases; Vaccine; Immunoconjugate; Peptidases; Vertebrata; Renin angiotensin system; Mammalia; Analog; Animal; Angiotensinogen; Hydrolases; Tentoxilysin; Angiotensin II
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1038/sj.bjp.0703178

Male, Sprague‐Dawley rats were actively immunized with novel angiotensin vaccines, and their pressor responses to exogenous angiotensin I (AI) and angiotensin II (AII) were assessed in vivo. Serum antibody titres were also measured. The most effective vaccine consisted of an AI analogue conjugated with a tetanus toxoid carrier protein and adjuvanted with aluminium hydroxide. When this vaccine was injected on days 0, 21 and 42, pressor responses to AI on day 63 were significantly inhibited (maximum, 8.9 fold shift), but responses to AII were unaffected. The anti‐angiotensin antibody titre was increased 32,100 fold, and, uniquely, these antibodies also cross‐reacted with angiotensinogen. These findings indicate that active immunization against AI may be a useful approach for treating cardiovascular disorders involving the renin‐angiotensin system. British Journal of Pharmacology (2000) 129, 1178–1182; doi:10.1038/sj.bjp.0703178