AT1 receptor agonistic antibodies, hypertension, and preeclampsia
Section snippets
Initial observations
Our interest in circulating mediators and an important place for angiotensin II (AII) in the preeclampsia equation stem from early observations that platelets from preeclamptic women have increased intracellular free calcium (Cai2+) concentrations and that these concentrations increase even further with AII stimulation, but not with thrombin.3 The phenomenon disappears after delivery. These increments in intracellular calcium levels also have been observed by others.4 Our initial study involved
Evaluating the role of AII
In the face of earlier observations that women with preeclampsia are markedly hyperresponsive to circulating AII7 and the findings we had observed earlier in the platelets,3 we were encouraged to direct our attention specifically toward AII. However, AII levels had been studied in detail in preeclamptic women by other investigators. In general, circulating AII levels were normal or even below normal in these studies. Moreover, the findings indicated that in preeclampsia, the activity of the
Exploring the roles of AT1-AA
We were aware of the fact that the notion of circulating AT1-AA would evoke much skepticism. We had not shown that AT1-AA might induce changes that contributed to preeclampsia. We next embarked on cellular observations to test the notion that AT1-AA can evoke signaling in vascular cells that could contribute to preeclampsia. Women with preeclampsia have an accelerated thrombotic tendency particularly in placenta, and tissue factor has been implicated in this process. We decided to focus on
Exploring the roles of AT1-AA
Much remains unknown about the nature of AT1-AA, its receptor binding properties, and subsequent signaling. We focused on the ability of the AT1-AA to recognize a specific conformation of the AT1 receptor.14 Cleavage of the external disulfide bond with dithiothreitol caused an inactivation of the receptor when stimulated either with AII or the autoantibodies in cultured neonatal rat cardiomyocytes. Long-term stimulation of the AT1 receptor with either agonist down-regulated the AT1
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Adaptations in autonomic nervous system regulation in normal and hypertensive pregnancy
2020, Handbook of Clinical NeurologyCitation Excerpt :More research is needed to confirm the findings of Aggarwal et al. (2017). AT1R-AA is functionally similar to AngII, and the latter could increase SNA through the AT1Rs in the CNS (Stein et al., 1984; Dechend et al., 2000, 2004, 2005, 2006; Ruzicka et al., 2013). Yet, there has been no evidence showing a direct central effect of AT1R-AA on sympathetic activity in animals or humans.
The renin-angiotensin system in 2011: New avenues for translational research
2011, Current Opinion in PharmacologyInhibiting B cell activating factor attenuates preeclamptic symptoms in placental ischemic rats
2023, American Journal of Reproductive ImmunologyB2 cells contribute to hypertension and natural killer cell activation possibly via AT1-AA in response to placental ischemia
2023, American Journal of Physiology - Renal PhysiologyPlacental Insufficiency/ Placenta-Associated Diseases
2023, The Placenta: Basics and Clinical Significance