Abstract 190: Angiotensin II Type 1A Receptor Expression by Catecholaminergic C1-neurons in the RVLM is Required for Full Development of Angiotensin Dependent Hypertension

Abstract

Objectives: Angiotensin II (Ang II) has a well established role in the development of hypertension via activation of the Ang II type 1A receptor (AT1AR). Whilst renal expression of this receptor is important for the hypertension, other sites appear to be involved. We tested the hypothesis that AT1ARs on catecholaminergic RVLM (C1) neurons are involved in Ang II-induced hypertension. Methods: Conditional deletion of AT1AR from C1 neurons was achieved by bilateral microinjections of a lentivirus expressing Cre-recombinase (Lv-PRSx8-Cre) under the control of a phox2 binding site promoter in the RVLM of AT1AR floxed mice. Control mice were injected with the same virus with a GFP transgene (Lv-PRSx8-GFP). Ang II (500ng/kg/minute) was infused subcutaneously via an osmotic minipump for 3 weeks. A noninvasive tail cuff system was used to record BP and heart rate (HR). Immunohistochemical localization of TH, GFP or the macrophage marker CD68 was performed using standard methods in sections from lentiviral microinjected mice. Results: Baseline systolic BP was not different between the groups (115±2 mmHg vs. 117±3 mmHg). However, infusion of Ang II induced a gradual pressor response that was greater in the Lv-PRSx8-GFP compared to the Lv-PRSx8-Cre injected mice (146±2 mmHg vs. 137±3 mmHg at day 11). The initial BP increase in the C1-selective AT1AR knockout mice was similar to the GFP mice, but a diversion in the BP response was observed after day 7. Post mortem analysis demonstrated that the lentiviral injections were within the region of the C1 neurons of the RVLM. Conclusions: These data demonstrate that AT1AR expression by catecholaminergic C1 neurons in the RVLM plays a role in the development of angiotensin-dependent hypertension.