Neuroinflammation and sympathetic overactivity: Mechanisms and implications in hypertension

Essential hypertension is a multifactorial disorder with a strong genetic predisposition. Although anti-hypertensive medications have drastically reduced cardiovascular diseases mortality and morbidity rates, a significant percentage of hypertensive individuals currently on anti-hypertensive therapy, remain hypertensive. In spite of the emergence of transgenic animals and sophisticated tools to study the pathophysiology of hypertension, unraveling the causal mechanisms remains a challenge. Research on borderline hypertensive humans and/or prehypertensive rat models revealed an elevation in centrally-mediated sympathetic activity and a heightened neuroinflammatory state. Hyperactive brain renin angiotensin system (RAS), oxidative stress and neuroinflammation in brainstem cardiovascular centers and other brain regions are implicated as key factors in augmenting sympathetic activity in hypertension and other cardiovascular abnormalities. Angiotensin (Ang) II, the main RAS effector peptide, has been shown to trigger significant upsurges in pro-inflammatory cytokines and reactive oxygen species (ROS). Both microglial and astroglial cells, via a host of different mechanisms, contribute to pro-inflammatory states and ROS generation in the brain. Hence, it becomes essential to understand the impact of Ang II and neuroinflammatory mediators on the impairment of cardioregulatory centers in the brain, and to investigate the role of glia in Ang II-mediated sympathoexcitation. Understanding the mechanisms leading to an elevation in neuroinflammatory states, and the possible ways of counteracting it, could aid in devising better therapeutic strategies for the treatment of cardiovascular diseases and hypertension. This review primarily focuses on the molecular aspects of hypertension from a neuroinflammatory standpoint within brainstem cardiovascular centers.