Increased AT1 receptor heterodimers in preeclampsia mediate enhanced angiotensin II responsiveness

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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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