Role of astrocytes in obesity-induced hypertension

Although obesity is a significant contributor to hypertension and cardiovascular disease, the mechanisms that connect excess adiposity to persistently elevated blood pressure extend far beyond peripheral metabolic and vascular changes. An increasing body of evidence suggests that a substantial component of this puzzle is disrupted autonomic regulation, specifically persistent activation of sympathetic pathways. This review explores the emerging role astrocytes play in this process. By controlling extracellular glutamate, ion balance, inflammatory signaling, energy metabolism, blood brain barrier integrity and neurovascular coupling, astrocytes normally contribute to the maintenance of neuronal and vascular homeostasis. However, exposure to excess nutrients, circulating fatty acids, adipokines and inflammatory mediators can interfere with these processes and cause astrocytes to become reactive. This change may increase oxidative and inflammatory signaling, hinder glutamate clearance, and disrupt the astrocyte-neuron communication in the cardiovascular regulatory centers of the brainstem and hypothalamus. The disturbance of excitatory amino acid transporter mediated glutamate homeostasis is specially concerning because it may intensify excitatory drive in autonomic circuits and sustain sympathoexcitation. In the context of obesity-associated hypertension, this review interconnects recent data to link metabolic dysfunction, neuroinflammation, central autonomic signaling, and astrocyte dysfunction. It also considers new therapeutic approaches targeted at restoring astrocytic balance. Targeting astrocyte-dependent pathways may provide a valuable supplementary strategy to address the neurogenic aspect of obesity-induced hypertension, even though several mechanistic questions remain unanswered.