Unlike drastic scenarios such as head trauma or stroke where an intracerebral pro-inflammatory response causes cell death, evidence indicates that the development of hypertension which is neurogenic in origin (chronic sympathoexcitation) involves a milder and persistent increase in intrinsic pro-inflammatory processes within brain cardiovascular control centers. In concert with this, it is also apparent that systemic pro-inflammatory responses that result from chronic hypertension can influence brain cardiovascular control centers, including significant activation of intracerebral pro-inflammatory mechanisms that ultimately affect blood pressure. Nonetheless, despite much progress towards a better understanding the pathophysiological processes in hypertension, many other questions remain to be answered. First and foremost is which of the above described scenarios comes first? For example, is the initiating factor high blood pressure that in turn activates, via systemic and intracerebral inflammation, mechanisms that result in chronic sympathoexcitation? Or, is the “chicken” the co-activation via the RAS of pre-autonomic and cerebral immune mechanisms that elicit chronic sympathoexcitation, and the “egg” the resulting hypertension and systemic immune activation that then feeds back to the brain to amplify the pro-immune cycle. Other questions remain, and include: (1) What are the contributions of brain cardiovascular control centers other than the PVN to the neuroinflammatory processes that contribute to hypertension? Is neuroinflammation in hypertension something that is peculiar to the PVN, or is it a generalized phenomenon for all brain centers that play a role in cardiovascular regulation. (2) How can the challenge of delivering drugs to the brain cardiovascular control centers across an impermeable BBB be solved, in order to design better treatment options for drug-resistant hypertensive patients? Or is this even necessary, as it has been shown that the BBB becomes leaky in chronic hypertension [27]?

One thing has become clear during the past few years, namely that enhanced neuroinflammation and overactivation of the RAS are major contributors to neurogenic hypertension. Hence, identifying the basic mechanisms involved in RAS-induced inflammation at cardioregulatory regions in the brain serves as a good starting point to further characterize the mechanisms underlying the onset and progress of this disease. To this end, while the majority of studies have focused on neuronal actions of Ang II/AT1R activation within the CNS on blood pressure control and hypertension, it is now well recognized that both Ang II and PRO can influence, directly or indirectly, the activity and immune function of both astrocytes and microglia [19, 31, 64]. Furthermore, as research indicates that controlling for inflammation is also favorable for hypertensive patients, should anti-inflammatory drugs be considered as a first line of defense in treating this condition? We present evidence that both microglia and astrocytes play a significant role in this disease thus making these cells a new therapeutic target when treating hypertension. Interestingly, despite the similarities between microglial and astrocyte activation, the contribution of astrocytes during RAS-induced hypertension, and to neuroinflammatory process and consequent blood pressure regulation during neurogenic hypertension has not been fully investigated.