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Increased AT1 receptor heterodimers in preeclampsia mediate enhanced angiotensin II responsiveness

Nature Medicine volume 7, pages 1003–1009 (2001)Cite this article

Abstract

Several examples of functional G-protein–coupled receptor heterodimers have been identified. However, it is not known whether receptor heterodimerization is involved in the pathogenesis of human disorders. Here we show that in preeclamptic hypertensive women, a significant increase in heterodimerization occurs between the AT1-receptor for the vasopressor angiotensin II and the B2-receptor for the vasodepressor bradykinin. AT1–B2-receptor heterodimerization in preeclampsia correlated with a 4–5-fold increase in B2-receptor protein levels. Expression of the AT1–B2 heterodimer increased the responsiveness to angiotensin II and conferred resistance in AT1-receptors to inactivation by reactive oxygen species raised in normotensive and preeclamptic pregnancies. We suggest that AT1–B2 heterodimers contribute to angiotensin II hypersensitivity in preeclampsia. Moreover, we identify preeclampsia as the first disorder associated with altered G-protein–coupled receptor heterodimerization.

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Figure 1: Detection of AT1 and B2 receptors on platelets.
Figure 2: AT1–B2-receptor heterodimerization on platelets.
Figure 3: Detection of AT1 and B2 receptors on omental vessels.
Figure 4: Angiotensin-II–stimulated G-protein activation on omental vessels.
Figure 5: Insensitivity of AT1–B2-receptor heterodimers to reactive oxygen species.

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Authors and Affiliations

  1. Medical Research Center, Ain Champs University Hospital, Cairo, Egypt

    Said AbdAlla & Adel el Massiery

  2. Heinrich-Pette-Institut, Hamburg, Germany

    Heinz Lother

  3. Institut für Pharmakologie und Toxikologie, Würzburg, Germany

    Ursula Quitterer

Authors
  1. Said AbdAlla
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  2. Heinz Lother
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  3. Adel el Massiery
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  4. Ursula Quitterer
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Correspondence to Ursula Quitterer.

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AbdAlla, S., Lother, H., el Massiery, A. et al. Increased AT1 receptor heterodimers in preeclampsia mediate enhanced angiotensin II responsiveness. Nat Med 7, 1003–1009 (2001). https://doi.org/10.1038/nm0901-1003

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