Abstract 154.

Circulating Ang II activates an aldosterone-MR-AT₁R pathway in the hypothalamus. To obtain insights into the actual aldosterone-MR- AT₁R neuronal pathway, the present study examined whether intra-PVN infusion of AAV-AT_1aR-siRNA or AAV-MR-siRNA prevents the Ang II induced increases in AT₁R and MR expression and BP. Two weeks sc infusion of Ang II at 500ng/kg/min in Wistar rats on regular salt diet increased BP by telemetry by 66 ± 3 mm Hg, and AT₁R and MR protein in the SFO, SON and PVN. Intra-PVN AT_1aR-siRNA decreased AT₁R but not MR expression in the PVN by sc Ang II, and MR-siRNA decreased MR but not AT₁R expression in the PVN. AT₁R and MR expression in both SFO and SON were not significantly changed by the two AAV-siRNA. Specific knockdown of AT₁R or MR in the PVN by AAV-siRNA prevented ~80% of the increase in BP induced by sc Ang II. These results suggest that circulating Ang II up-regulates brain Ang II and aldosterone and increases MR and AT₁R in the SFO, SON and PVN. Prevention of Ang II induced increases in MR but not AT₁R by knockdown of MR and vice versa suggests an independent regulation of MR and AT₁R in the PVN. Both AT₁R and MR in the PVN play a critical role in Ang II-induced hypertension in rats.∗ p<0.05 versus AAV-SCM alone. a: p<0.05 versus AAV-SCM + Ang II. [ABSTRACT FROM AUTHOR]