Abstract 154: Knockdown of Mineralocorticoid or AT1 Receptor Gene in the Paraventricular Nucleus Prevents Ang II Induced Hypertension in Rats

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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-AT1aR-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 AT1aR-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.

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