Angiotensin-II, the Brain, and Hypertension: An Update.

Abstract

Despite enormous therapeutic advancements, the incidence of hypertension continues to rise1 and remains a medical burden of global proportions.2 This is likely due, in part, to the complex pathogenesis of hypertension.1 In addition to pathological processes in peripheral cardiovascular organs, the central nervous system (CNS) has emerged as a major culprit. The renin–angiotensin system (RAS) plays a crucial role in cardiovascular control, and both systemic angiotensin-II (Ang-II) and centrally generated Ang-II signal through complex neural networks to contribute to the development of hypertension (Figure). Although the effects of Ang-II within the brain are multifaceted, several key hypertensive players have emerged, including oxidative stress, endoplasmic reticulum stress, inflammation, and transcription factor activation. The purpose of this review is to provide a brief update on recent work related to Ang-II, the brain, and hypertension with a specific focus on Hypertension articles when appropriate. Figure. Simplified schematic illustrating the signaling pathways ( top box), as well as neural networks and sympathetic nervous system influenced physiological outputs ( middle box) involved in the development of hypertension due to peripherally or locally generated angiotensin-II (Ang-II) action in the brain. Common animal models used to evaluate Ang-II, the brain, and hypertension are also highlighted ( bottom box). See text for additional details. AP indicates area postrema; AP-1, activator protein-1; AT1aR, angiotensin type 1a receptor; CVLM, caudal ventral lateral medulla; DOCA, deoxycorticosterone acetate; ER, endoplasmic reticulum; EP1R, prostaglandin E receptor 1; IML, intermediolateral nucleus; MnPO, median preoptic nucleus; NAD(P)H, nicotinamide adenine dinucleotide phosphate; NTS, nucleus tractus solitarii; NF-κB, nuclear factor-κB; OVLT, organum vasculosum lamina terminalis; PP, posterior pituitary; PVN, paraventricular nucleus of the hypothalamus; ROS, reactive oxygen species; RVLM, rostral ventral lateral medulla; SFO, subfornical organ; SHR, spontaneously hypertensive rat; and SON, supraoptic nucleus. Dysregulation of the RAS is common in human hypertension,3 …