Herlitz H, Fu MLX, Wallukat G, Muller-Esterl W, Hjalmarson A,
Aurell M
Functional autoantibodies against angiotensin II receptor subtype 1
(AT1) in patients with malignant hypertension
Am Soc Nephrol
J Am Soc Nephrol (abstract)
(Sep) 7:1562 1996
Hypertension is a catastrophic condition in which target organ damage
can be debilitating and even lethal. This condition arises in many
different illnesses but is particularly important in the US
African-American population which accounts for most of the cases seen
in the US. The pathogenesis of this condition is complex; however
clinical studies suggest that angiotensin II plays an important role.
In this study Herlitz et al report on the antibody specificity and
functional characteristics of autoantibodies to angiotensin II subtype
1 receptors harvested from the plasma of patients with malignant
hypertension (present in 40% of their cases). Sera containing
autoantibodies from patients with malignant hypertension reacted with
AT1 but not AT2 or bradykinin receptor peptides. Further IgG
autoantibodies displayed a dose-dependent chronotropic effect in
cultured neonatal cardiomyocytes, similar to the effect of AII. The
positive chronotropic effect was blocked by losartan in one case and
by prazosin + losartan in another; however there was no effect of AT2
blockade on the chronotropic effect. The effect of the antibody was
dose-dependent, sustained and did not show desensitization in the
cultured cardiomyocyte assay.
The authors concluded that anti-AT1 autoantibodies found in patients
with malignant hypertension were monospecific to AT1 receptors are
agonistic and their chronotropic effect is non-desensitizing. This is
an exciting preliminary report in that the possibility that malignant
hypertension could be at least in part an autoimmune syndrome in these
cases.
Comment: The patient population source for these antibodies was
not identified in this report so it is possible that the patients had
underlying autoimmune diseases known to be associated with malignant
hypertension (e.g. scleroderma, PAN). Still, this is a potentially
important finding. It would be of great interest to determine whether
this antibody binds to receptors and has agonistic effects on vascular
smooth muscle cells (contraction and cell hypertrophy/hyperplasia) or
endothelial cells since vascular hypertrophy and hyperplasia are
prominent features in the vasculature of patients with malignant
hypertension.
(Robert D. Toto, M.D., University of Texas Southwestern Medical
Center)
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Am Soc Nephrol
H: Drug therapy :
Acute hypertensive crisis
H: Pathophysiology :
Vascular pathology