Abstract 18118: Overexpression of Angiotensin-Converting Enzyme 2 in the Rostral Ventrolateral Medulla Inhibits the Neuroinflammation in Hypertensive Rats

Abstract

Neuroinflammation has been reported to contribute to cardiovascular dysfunction in hypertension. Gene transfer of angiotensin-converting enzyme 2 (ACE2) into the rostral ventrolateral medulla, a key region for controlling the sympathetic outflow, leads to a significant reduction in blood pressure and sympathetic activity in hypertension. The goal of the present work is to determine the effect of ACE2 overexpression in the RVLM on neuroinflammation in spontaneously hypertensive rats (SHRs). SHRs was received lentiviral-mediated overexpression of ACE2 (lenti-ACE2) or lenti-enhanced green fluorescent protein (lenti-GFP) control. It was found that a significant reduction in blood pressure and heart rate in the SHRs 3 weeks after lenti-ACE2 injected into the RVLM. Activation of microglia in the RVLM was confirmed in the SHR-GFP, but it was significantly reduced in SHR-ACE2. Content and mRNA expression of the proinflammatory cytokine interleukin-1 beta, interleukin-6, and tumor necrosis factor-alpha in the RVLM was significantly (P<0.05) decreased in the SHRs that treated with injection of lenti-ACE2 compared with lenti-GFP. In normotensive WKY rats, we also found that overexpression of ACE2 in the RVLM significantly (P<0.05) reduced the increases in mRNA expression of interleukin-1 beta, interleukin-6, and tumor necrosis factor-alpha evoked by intracerebraventricular infusion of lipopolysaccharides (4 weeks). Based on the present data, it is suggested that ACE2 gene transfer into the RVLM inhibits neuroinflammation in hypertensive rats, which may be responsible for the beneficial effects of central ACE2 on hypertension. (This work is supported by NSCF 81070214 and 81170240).