Abstract 058: ACE2 Ubiquitination Regulates Neuronal Activity In Hypertension
| Autor: | Mazher Mohammed, Mona Elgazzaz, Xinping Yue, Catalin Filipeanu, Eric D Lazartigues |
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| Rok vydání: | 2022 |
| Předmět: | |
| Zdroj: | Hypertension. 79 |
| ISSN: | 1524-4563 0194-911X |
| DOI: | 10.1161/hyp.79.suppl_1.058 |
| Popis: | ACE2 expression on GABAergic neurons could maintain the inhibitory tone over pre-sympathetic neurons in the paraventricular nucleus (PVN) and thus contribute to the regulation of blood pressure (BP). Here we investigated the role of ACE2 ubiquitination in the bed nucleus of the stria terminalis (BNST), a region containing GABAergic neurons and involved in cardiovascular responses to stress. C57BL6/J male mice were injected in the BNST with a ubiquitination-resistant human ACE2 mutant (AAV-hACE2-5R). A subset of mice was also injected with AAV-GCaMP6s-eYFP in the PVN and BNST to record intracellular Ca 2+ activity via fiber photometry. After 6 weeks, the mice were chronically infused with Ang-II (600 ng/kg/min) for 2 weeks while BP was monitored by telemetry. Ang-II-infusion resulted in a significant increase in mean BP compared to controls (152±7 vs. 123±4 mmHg, respectively; n=6, pA antagonist, 1 mmol/L in 100nL) in the PVN produced a blunted BP rise in Ang-II-infused mice compared to controls (AUC: 261±36 vs. 392±45, respectively; n=4, p2+ mediated fluorescence in the PVN and a parallel reduction of neuronal activity in the BNST (ΔF/F 0 : +0.9±0.02 and -0.1±0.03; respectively). Surprisingly, hACE2-5R expression in the BNST produced a rapid and persistent inhibition of neuronal activity. Capillary Western analysis showed a 3-fold increase in NEDD4-2 (n=4, p |
| Databáze: | OpenAIRE |
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