No Brain Renin–Angiotensin System
Déjà vu All Over Again?
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See related article, pp 1136–1144
Few would argue that the renin–angiotensin system (RAS) is the most extensively studied regulatory pathway controlling arterial blood pressure. That its inhibition remains a key target of the current antihypertensive therapy strongly evidences the sustained clinical importance of the system. Since its initial discovery nearly 120 years ago, new components and mechanisms of the RAS are discovered with uncommon regularity. Thus, the RAS, once thought elegant in its simplicity, is now considered one of the most complex regulators of blood pressure and electrolyte homeostasis. Adding to this inherent complexity is the simultaneous action of the endocrine and tissue RAS, functional interaction among the various tissue RAS, and the activity of counter-regulatory peptides and receptors within this system.1 In particular, the RAS in the brain is further complicated by the intricate neural circuitry between cardiovascular, fluid homeostasis, and metabolic control regions where a large number of studies support not only the actions of angiotensin peptides but also the capacity for their local generation. As addressed in a previous 2006 Editorial Commentary in Hypertension, molecular techniques are required for manipulation of specific cell types in brain expressing RAS components to address what was controversial then and remains controversial now, specifically, how are the components configured to exert its well-known functional effects?2
There is extensive evidence for the existence and function of all components of the RAS in brain that goes back several decades and reflects studies in almost every species including humans, dogs, sheep, rats, and mice.1 Although impossible to accurately cite the thousands of articles on this topic in the context of this short editorial, evidence supporting a central local brain RAS can be broadly divided into 2 types. First, there is compelling evidence for the de novo production of all components …