Mechanism of agonistic angiotensin II type I receptor autoantibody-amplified contractile response to Ang II in the isolated rat thoracic aorta.

Abstract

Agonistic autoantibody to the angiotensin II type I receptor (AT1-AA) is highly associated with preeclampsia by increasing the sensitivity of Ang II during pregnancy in rats, thus leading to a preeclampsia-like syndrome. However, the mechanism underlying this phenomenon remains unclear. The purpose of this study was to observe AT1-AA amplification of Ang II-induced vasoconstriction in rat thoracic aortic rings. It was found that exposure to low concentrations of AT1-AA (0.4 nM) caused a contraction of <5% of the maximal response to 60 mM KCl. In addition, the Ang II-induced contractile response was amplified in the presence of a threshold contraction to AT1-AA, as manifested by a leftward shift of the midpoint of the concentration-response curve with no change in the maximal response. These results showed that preincubation with low AT1-AA could amplify the Ang II dose-response curve, and this amplification could be attenuated markedly by 0.1 µM heptapeptide AFHYESQ. In calcium-free Krebs solution, 10 µM of 2-aminoethoxydiphenyl borate (an IP3 receptor inhibitor) both blocked the AT1-AA base contraction and completely abolished the amplification. Both 5 µM of U-73122 (a phospholipase C inhibitor) and 10 µM of εV1-2 (an εPKC inhibitor) could partially inhibit the Ang II-induced contractile response. εV1-2, but not U-73122, could completely inhibit the amplification response of AT1-AA to Ang II. These results suggest that AT1-AA is able to cause amplification response to Ang II probably via the calcium-independent protein kinase C pathway, which may provide a new therapy strategy for preeclampsia.

• Authors: Wenhui Zhang, Yanqian Zheng, Fang Liu, Xiaofang Wang, Zhu Jin, Jianming Zhi
• Journal: Acta biochimica et biophysica Sinica (Acta Biochim Biophys Sin (Shanghai)) Vol. 47 Issue 10 Pg. 851-6 (Oct 2015) ISSN: 1745-7270 [Electronic] China
• PMID: 26350097 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © The Author 2015. Published by ABBS Editorial Office in association with Oxford University Press on behalf of the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences.

Chemical References

• Autoantibodies
• Receptor, Angiotensin, Type 1
• Angiotensin II

Topics

• Angiotensin II (administration & dosage)
• Animals
• Aorta, Thoracic (drug effects, immunology)
• Autoantibodies (immunology)
• Dose-Response Relationship, Drug
• In Vitro Techniques
• Muscle Contraction (drug effects, immunology)
• Muscle, Smooth, Vascular (drug effects, immunology)
• Rats
• Rats, Wistar
• Receptor, Angiotensin, Type 1 (immunology)
• Vasoconstriction (drug effects, immunology)