
<ArticleTitle>Increased <prot>AT(1) receptor</prot> heterodimers in preeclampsia mediate enhanced <prot>angiotensin II</prot> responsiveness.</ArticleTitle>
<AbstractText>Several examples of functional <prot><prot>G-protein</prot>-coupled receptor</prot> 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 <prot>AT(1)-receptor</prot> for the vasopressor <prot>angiotensin II</prot> and the <prot>B(2)-receptor</prot> for the vasodepressor <prot>bradykinin</prot>. <prot>AT(1)-B(2)-receptor</prot> heterodimerization in preeclampsia correlated with a 4-5-fold increase in <prot>B(2)-receptor</prot> protein levels. Expression of the <prot>AT(1)-B(2)</prot> heterodimer increased the responsiveness to <prot>angiotensin II</prot> and conferred resistance in <prot>AT(1)-receptor</prot>s to inactivation by reactive oxygen species raised in normotensive and preeclamptic pregnancies. We suggest that <prot>AT(1)-B(2)</prot> heterodimers contribute to <prot>angiotensin II</prot> hypersensitivity in preeclampsia. Moreover, we identify preeclampsia as the first disorder associated with altered <prot><prot>G-protein</prot>-coupled receptor</prot> heterodimerization.</AbstractText>
