Central Angiotensin II ‐ induced hypertension downregulates AT2R and the mir‐29 family in rats

Abstract

Ang II plays a critical role in the pathogenesis of hypertension by enhancing sympathetic outflow via the AT1R. However, the role of AT2R in this process is not clear. The data from our lab revealed an inhibitory influence of AT2R on sympathetic tone. Mir‐29 is predicted to regulate AT2R expression. We hypothesized that the decreased AT2R expression may contribute to hypertension induced by central infusion of Ang II by a mechanism dependent on mir‐29. Male rats received icv infusion of Ang II (50 ng/min) for 7 days. Blood pressure (BP) and heart rate (HR) were measured by telemetry. On day 7, the brain was removed to evaluate protein and mir‐29. As expected, the rats receiving Ang II exhibited an increased BP (38.1 ± 5.2 mmHg) and HR (86.3 ± 11.5 bpm) and an up‐regulated AT1R. In addition, (1) icv Ang II significantly downregulated AT2R protein in PVN and RVLM by 39.2 ± 3.7% and 64.1 ± 4.4%; (2) Gαi2 and nNOS, two downstream signal molecules activated by the AT2R, were significantly down regulated; (3) The expression of mir‐29a and mir‐29b, two potential regulators of AT2R protein, were decreased by 37.5 ± 4.1% and 32.8 ± 2.8%. (4) All of the above alterations were abolished by Losartan. These results suggest that, in the brain, the down regulated AT2R and its downstream signaling pathways contribute to Ang II induced hypertension. The decreased AT2R may be attributable to the inhibition of mir‐29 family by Ang II. Supported by HL093028.