Abstract 82: In Vivo Memri Reveals Persistent Activation of the Pvn by an Acute Systemic Angiotensin Ii Injection
Introduction: An overactive brain renin-angiotensin system is a major factor in the establishment of neurogenic hypertension in the spontaneously hypertensive rat (SHR). However, there is no concrete evidence to indicate that this is associated with enhanced neuronal activity in the brain. The objective here was to use the MRI to establish the effect of ANGII on neuronal activity in the autonomic brain areas. We propose that a single ANGII injection will cause a long-lasting neuronal response in the autonomic brain areas, which will be exaggerated in the SHR.
Methods: In vivo basal and ANGII-evoked neuronal activity was measured in the Wistar-Kyoto (WKY) rat and the SHR using manganese-enhanced MRI (MEMRI) at 4.7Tesla. Rats were treated with manganese chloride (MnCl2 30 mM solution, i.p.;16-20 hrs prior to the MRI), which labels active neurons. T1-weighted images were obtained 16-20 hrs after a single ANGII injection (0.32μg/kg i.p.). Coronal slice scans (caudally from end of the cerebellum towards the hypothalamus) were processed using itkSNAP, and data analyzed for normalized signal intensity.
Results: Acute ANGII injection caused an immediate pressor response in the WKY (ΔSBP=∼20mmHg), normalizing within 2 hours. Despite this, ANGII evoked a persistent PVN neuronal activation, which was elevated by 22±4% in the WKY, and by 187±45% in the PVN of SHR. As a result, there was a ∼8.5fold increase in the ANGII-dependent neuronal activity in the PVN of SHR compared to WKY. Furthermore, there was a ∼2.5fold decrease in the NTS neuronal activity in the SHR compared to WKY.
Conclusion: The present study shows for the first time the correlation between ANGII and autonomic neuronal activation. Even a single systemic ANGII injection results in a lasting effect on the brain. This is particularly apparent in the SHR, which exhibited an exaggerated neuronal response to the ANGII stimulus, reflected in the elevated PVN neuronal activation corresponding to the enhanced sympathetic drive, and in the depressed NTS activation corresponding to the dysfunction in the barorereflex processing. Thus, repeated pro-hypertensive stimuli in the autonomic brain areas may lead to pre-sympathetic neuronal plasticity, resulting in heightened sympathetic drive and hypertension.
- © 2012 by American Heart Association, Inc.