SOD1 overexpression in paraventricular nucleus improves post-infarct myocardial remodeling and ventricular function

Abstract

Excessive sympathetic activation contributes to the progression of chronic heart failure. Reactive oxygen species in paraventricular nucleus (PVN) play an important role in the enhanced sympathetic outflow. This study was designed to determine whether superoxide dismutase 1 (SOD1) overexpression in the PVN attenuated the sympathetic activation and cardiac dysfunction in rats after an episode of myocardial infarction (MI). Adenoviral vectors containing human SOD1 (Ad-SOD) or null adenoviral vectors (Ad-null) were immediately microinjected into the PVN of rats with coronary artery ligation or sham operation. At the eighth week, the SOD1 protein level and activity in the PVN increased while the superoxide anions in the PVN decreased in Ad-SOD rats. The SOD1 overexpression in the PVN prevented the increases in left ventricular end-diastolic pressure and volume, and the decreases in ejection fraction and peak velocities of contraction in MI rats. In addition, there was an attenuation of renal sympathetic nerve activity, cardiac sympathetic afferent reflex and plasma norepinephrine level in MI rats. Furthermore, the SOD1 overexpression in the PVN reduced cardiomyocyte size, collagen deposition and the TUNEL-positive cardiomyocytes in MI rats. These results indicate that the SOD1 overexpression in the PVN attenuates the excessive sympathetic activation, myocardial remodeling, cardiomyocyte apoptosis and ventricular dysfunction in MI rats.

Hydrogen Sulfide in Paraventricular Nucleus Enhances Sympathetic Activity and Cardiac Sympathetic Afferent Reflex in Chronic Heart Failure Rats

“…Previous studies have shown that PVN is involved in excessive sympathetic activation and enhanced CSAR in CHF [17]–[20]. CBS expression has been found in the PVN [21].…”

Cardiac sympathetic afferent reflex and its implications for sympathetic activation in chronic heart failure and hypertension

“…SOD1 overexpression in the PVN in rats with coronary ligation‐induced CHF not only inhibited CSAR and sympathetic outflow, but also improved myocardial remodelling and ventricular function (Gao et al . ). Similarly, long‐term oral administration of tempol for 6 weeks attenuated ventricular dysfunction, normalized the CSAR, sympathetic outflow and the RSNA response to Ang II in the PVN, and reduced superoxide anion level and AT 1 receptor expression in the PVN and RVLM (Shi et al .…”

“…The importance of enhanced CSAR is supported by other findings that the superoxide dismutase (SOD) overexpression in the PVN (Gao et al . ), long‐term oral administration of tempol (Shi et al . ) or electroacupuncture (Ma et al .…”

γ‐aminobutyric acid‐mediated neurotransmission in cerebellar–hypothalamic circuit attenuates gastric mucosal injury induced by ischemia‐reperfusion

“…It is well known that inhibiting sympathetic activity ameliorate organ ischemia-reperfusion injury and is associated with cellular apoptosis. 41,42 We consider that the sympathetic inhibition caused by FN stimulation partially contributes to the improvement of gastric ischemia-reperfusion injury and gastric mucosal cell apoptosis. In this study, we found that FN stimulation attenuated the GSN activity and enhanced GMBF.…”