Evaluation of PI3K expression and its interaction with angiotensin II on central autonomic nuclei of hypertensive animals

Abstract

There is evidence that PI3K protein is directly linked to the intracellular signaling of the angiotensin II (ANG II) pathways (via AT1 receptors) that act as a neuromodulator of autonomic outflow in spontaneous hypertensive rats (SHR). In the present study we evaluate the difference on the PI3K expression as well as its interaction with ANGII in the PVN, NTS and RVLM of SHR compared to WKY and wistar rats. Immunoblotting was performed to quantify the regulatory subunit p85 of the PI3K and phosphorilated PKB (active form) in the PVN, NTS and RVLM of SHR and normotensive rats. Moreover, we also evaluated the role of ANG II and its interaction with PI3K at the PVN level in regulating the lumbar sympathetic nerve activity (LSNA) by using an in situ arterially perfused preparation. The expression of p85 subunit did not differ among all nuclei studied at any experimental group, but the phosphorilated PKB was significantly more expressed in the PVN of SHR (1.5x) when compared to wistar and WKY. ANG II (10 μM) microinjected into the PVN elicited an increase in LSNA (18%), which was attenuated at 5 min after LY294002 (50 μM) microinjected into the same site (2%), with recovering 20 min later (17%). If there is any interaction between ANG II and PI3K pathway related to hypertensive stage it seems that PVN is the pivotal autonomic nucleus involved in the sympathoexcitation of this pathology.Research Support: FAPESP, CAPES and CNPQ.