Influence of active immunization against angiotensin AT1 or AT2 receptor on hypertension development in young and adult SHR.
The influence of long-lasting blockade of angiotensin AT1 or AT2 receptors by antibody against the particular receptor peptides on blood pressure and relative heart and kidney weight was studied in spontaneously hypertensive rats (SHR). Young and adult SHR were repeatedly immunized against the sequence 14-23 of angiotensin AT1 receptor from the age of either 1 or 3 months. Other groups of young and adult SHR were immunized against the sequences 37-43 and 106-116 of angiotensin AT2 receptor. Synthetic peptides conjugated to bovine gamma globulin were used as antigens. After 5 months of immunization, blood pressure was measured by the direct method. All immunized animals produced antibodies against the particular peptides. At the end of immunization, the blood pressure was significantly decreased in SHR immunized in youth against angiotensin AT1 receptor peptide, although no difference in heart and kidney hypertrophy was observed compared to sham-immunized SHR. The immunization against angiotensin AT1 receptor peptide in adulthood as well as the immunization against angiotensin AT2 receptor peptides in youth or in adulthood affected neither blood pressure nor heart and kidney weight. No influence of immunization on the studied parameters was observed in normotensive WKY rats. Angiotensin AT1 receptors play a more important role in the pathogenesis of spontaneous hypertension than angiotensin AT2 receptors. The blockade of angiotensin AT1 receptors by active immunization against the receptor peptide attenuated hypertension development in young SHR but did not modify the already established hypertension in adult SHR.
Zelezná
B
B
Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Prague.
Veselský
L
L
Velek
J
J
Dobesová
Z
Z
Zicha
J
J
Kunes
J
J
D000375:Aging; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D006973:Hypertension / Q000473:pathology / Q000503:physiopathology*; D006984:Hypertrophy; D007668:Kidney / Q000473:pathology; D009206:Myocardium / Q000473:pathology; D009929:Organ Size; D010446:Peptide Fragments / Q000276:immunology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000276:immunology / Q000502:physiology*; D014611:Vaccination
D057911:Angiotensin Receptor Antagonists; D010446:Peptide Fragments; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin