Abstract MP05: Mineralocorticoid And Angiotensin II Type 1 Receptors In The Subfornical Organ Mediate Angiotensin II Hypertension In Rats
Circulating Ang II increases BP through both peripheral and central mechanisms. Activation of both AT1R and MR in the CNS plays a critical role in Ang II-induced hypertension. The subfornical organ (SFO) contains both MR and AT1R and can relay the signals of circulating Ang II to downstream nuclei such as the PVN. In this study, we evaluated the effect of intra-SFO infusion of AAV-MR-siRNA or AAV-AT1aR-siRNA on MR or AT1R mRNA expression in the SFO and PVN and Ang II induced hypertension as assessed by telemetry. Two week sc infusion of Ang II at 500 ng/kg/min in Wistar rats on regular salt diet increased BP by 60~65 mmHg. This pressor effect of Ang II was largely prevented by AAV-MR-siRNA or AAV-AT1R-siRNA in the SFO (Figure). Ang II increased AT1R mRNA expression (1.7± 0.4 vs 0.8 ± 0.04 х10-1, p<0.05) in the SFO. Both MR- and AT1R-siRNA in the SFO prevented this increase (1.1 ± 0.2х10-1 and 1.0± 0.3х10-1). In contrast, Ang II decreased MR mRNA expression (3.2 ± 0.2 vs. 4.1 ± 0.2х10-2, p<0.05) in the SFO. Both MR- and AT1R-siRNA further decreased MR mRNA expression (2.7 ± 0.2 х10-2 and 2.3 ± 0.3 х10-2). In the PVN, Ang II increased AT1R mRNA by ~100% and MR mRNA by ~20%. Only AT1R-siRNA in the SFO prevented these increases in the PVN. AAV mediated eGFP fluorescence expression was observed in the SFO but not the PVN. These results suggest that circulating Ang II differentially regulates MR and AT1R expression in the SFO. Prevention of Ang II induced AT1R up-regulation by knockdown of either AT1R or MR suggests a MR dependent regulation of AT1R in the SFO. MR-AT1R signaling in the SFO appears to play a major role in Ang II-induced hypertension in rats.
* p<0.05, vs. baseline values; a: p<0.05, vs. AAV-SCM-siRNA
Author Disclosures: H. Wang: None. B.S. Huang: None. A. Chen: None. M. Ahmad: None. F.H. Leenen: None.
- © 2014 by American Heart Association, Inc.