Abstract 81: Activation of Microglia in the PVN Precedes Increase in Blood Pressure in Chronic Angiotensin II Infusion Rat Model of Hypertension
Introduction: Hypertension is the most important risk factor for cardiovascular disease. Dysregulation of the autonomic nervous system (ANS) with increased sympathetic stimulation is a hallmark of neurogenic hypertension, and has been shown to precede the rise in the blood pressure. We have previously shown that chronic Angiotensin II (Ang II) infusion increases blood pressure by activation of the microglia in the cardioregulatory brain regions, such as the paraventricular nucleus of the hypothalamus (PVN). Here, we studied the activation of microglia following 3- and 7-day Ang II infusion as a marker of neuroinflammation. We hypothesize that activation of the microglia in the PVN is a possible precursor to the ANS dysfunction and the blood pressure increase in Ang II-dependent hypertension.
Methods: An osmotic minipump delivering either saline or 200ng/kg/min Ang II S.C. was implanted in 9-week old adult male Sprague-Dawley rats randomly assigned to control (saline), or 3-day or 7-day Ang II infusion (n=4) . Blood pressures were measured using radiotelemetry. CD11b immunoblotting of the PVN was used to assess the activated microglia in the PVN. Additionally, Iba1 immunohistochemistry of the PVN was used to image and quantify the increase in total size and number of activated microglia.
Results: Despite no significant change in the blood pressure, we found a 1.40 fold increase in the CD11b protein quantity, and a 12% increase in microglia size at 3-days of Ang II infusion compared to control. At 7-days of Ang II infusion, we observed a 4.93 fold increase in the CD11b protein quantity, a 33% increase in microglia size, and a 29% higher number of microglia, which was accompanied by ∼ 25mmHg elevation in the blood pressure compared to control.
Conclusion: These data suggests that microglia in the PVN become activated in as early as 3-days following Ang II infusion, before the blood pressure changes occur. Therefore, activation of microglia precedes the increase in blood pressure. This implicates the microglia in the dysregulation of the ANS in Ang II hypertension.
- © 2012 by American Heart Association, Inc.