Cardiovascular disease prevalence rises rapidly after menopause, which is believed to be derived from the loss of estrogen. It is reported that sympathetic tone is increased in postmenopause. The high level of oxidative stress in the rostral ventrolateral medulla (RVLM) contributes to increased sympathetic outflow. The focus of this study was to determine if estrogen replacement reduces oxidative stress in the RVLM and sympathetic outflow in the ovariectomized (OVX) rats. The data of this study showed that OVX rat increased oxidative stress in the RVLM and sympathetic tone; estrogen replacement improved cardiovascular functions but also reduced the level of oxidative stress in the RVLM. These findings suggest that estrogen replacement decreases blood pressure and sympathoexcitation in the OVX rats, which may be associated with suppression in oxidative stress in the RVLM through downregulation of protein expression of NADPHase (NOX4) and upregulation of protein expression of SOD1. The data from this study is beneficial for our understanding of the mechanism of estrogen exerting cardiovascular protective effects on postmenopause.

The rostral ventrolateral medulla (RVLM) plays a key role in cardiovascular regulation. It has been reported that tonically active glutamatergic input to the RVLM is increased in hypertensive rats, whereas angiotensin-converting enzyme 2 (ACE2) in the brain has been suggested to be beneficial to hypertension. This study was designed to determine the effect of ACE2 gene transfer into the RVLM on tonically active glutamatergic input in spontaneously hypertensive rats (SHRs). Lentiviral particles containing enhanced green fluorescent protein (lenti-GFP) or ACE2 (lenti-ACE2) were injected bilaterally into the RVLM. Both protein expression and activity of ACE2 in the RVLM were increased in SHRs after overexpression of ACE2. A significant reduction in blood pressure and heart rate in SHRs was observed 6 wk after lenti-ACE2 injected into the RVLM. The concentration of glutamate in microdialysis fluid from the RVLM was significantly reduced by an average of 61% in SHRs with lenti-ACE2 compared with lenti-GFP. ACE2 overexpression significantly attenuated the decrease in blood pressure and renal sympathetic nerve activity evoked by bilateral injection of the glutamate receptor antagonist kynurenic acid (2.7 nmol in 100 nl) into the RVLM in SHRs. Therefore, we suggest that ACE2 overexpression in the RVLM attenuates the enhanced tonically active glutamatergic input in SHRs, which may be an important mechanism underlying the beneficial effect of central ACE2 to hypertension.

The imbalance between angiotensin II (Ang II) and angiotensin 1–7 (Ang 1–7) in the brain has been reported to contribute to cardiovascular dysfunction in hypertension. Exercise training (ExT) is beneficial to hypertension and the mechanism is unclear. This study was aimed to determine if ExT improves hypertension via adjusting renin angiotensin system in cardiovascular centers including the rostral ventrolateral medulla (RVLM). Spontaneously hypertensive rats (SHR, 8 weeks old) were subjected to low-intensity ExT or kept sedentary (Sed) for 12 weeks. Blood pressure elevation coupled with increase in age was significantly decreased in SHR received ExT compared with Sed. The results in vivo showed that ExT significantly reduced or increased the cardiovascular responses to central application of sarthran (antagonist of Ang II) or A779 (antagonist of Ang 1–7), respectively. The protein expression of the Ang II acting receptor AT1R and the Ang 1–7 acting receptor Mas in the RVLM was significantly reduced and elevated in SHR following ExT, respectively. Moreover, production of reactive oxygen species in the RVLM was significantly decreased in SHR following ExT. The current data suggest that ExT improves hypertension via improving the balance of Ang II and Ang 1–7 and antioxidative stress at the level of RVLM.

The current data demonstrate that GABAergic mechanisms in the RVLM are responsible for the hypotension and sympathoinhibition of moxonidine.

The centrally antihypertensive drug moxonidine decreases ROS production in the RVLM through inactivation of the PI3K/Akt signaling pathway in hypertension.