[Immunologic approach of the blockage of the renin angiotensin system in vivo].
To block the renin-angiotensin system by antibodies directed against renin or angiotensins is an old and recent goal. This goal can be attained by passive transfer of antibodies or by active immunization against the different molecules of the system. Only passive transfer of polyclonal antibodies directed against the native substrate (angiotensinogen) has been performed in rats. This acute blockade of angiotensinogen substrate availability decrease blood pressure about 30 mmHg in salt depleted rats. Passive transfer of anti-converting enzyme immunoglobulins has been already performed in rabbit and rat. It induced an immunoallergic reaction in the pulmonary capillary bed. Immunization against angiotensin II has been a powerful tool in the exploration of the role of the renin angiotensin system in hypertension. Passive and active immunization have been performed in different species: rabbit, rat. The majority of the results concerning the decrease in blood pressure was negative. However, some works reported positive results which could be related to the high affinity of antibodies for angiotensins. Passive and active immunizations against renin were also performed in different species: dog, pig, rat, rabbit, primates. The majority of the results concerning the decrease of blood pressure were positive, if species specificity of renin was taken into account. Recently passive transfer of polyclonal and monoclonal antibodies, directed against human renin have been performed in normotensive and hypertensive primates, demonstrating an acute fall in blood pressure comparable to that observed with converting enzyme inhibitors. Active immunization against human renin has also been performed in primates; and the chronic blockade of the renin-substrate reaction obtained in this way was associated with a significant decrease in blood pressure, aldosterone secretion and a disappearance of plasma renin activity. Unfortunately, such an active immunization was associated with an organ specific autoimmune disease within the kidney. In conclusion, passive and active immunization against the different proteins and peptides of the system offers specific models of blockade which can be compared with synthetic inhibitors of renin, converting enzyme and angiotensins. Therapeutic application of this immunological approach necessitates the verification of the total absence of autoimmune disease.
Michel
J B
JB
INSERM U 36, Paris.
Sayah
S
S
Guettier
C
C
Reade
R
R
Gardes
J
J
Galen
F X
FX
Carelli
C
C
Corvol
P
P
D000808:Angiotensinogen / Q000276:immunology / Q000502:physiology; D000809:Angiotensins / Q000276:immunology / Q000502:physiology; D000818:Animals; D000906:Antibodies / Q000276:immunology; D006801:Humans; D007114:Immunization; D007116:Immunization, Passive; D007158:Immunologic Techniques; D007703:Peptidyl-Dipeptidase A / Q000276:immunology / Q000502:physiology; D012083:Renin / Q000276:immunology / Q000502:physiology; D012084:Renin-Angiotensin System
D000809:Angiotensins; D000906:Antibodies; D000808:Angiotensinogen; D007703:Peptidyl-Dipeptidase A; D012083:Renin
Approche immunologique du blocage du système rénine angiotensine in vivo.