Glutamatergic Regulation of Hypothalamic Presympathetic Neurons in Hypertension

Elevated sympathetic vasomotor tone emanating from the brain is a major mechanism involved in the development of hypertension. Increased glutamatergic excitatory input to presympathetic neurons in the paraventricular nucleus (PVN) of the hypothalamus leads to increased sympathetic outflow in various animal models of hypertension. Recent studies have revealed molecular and cellular mechanisms underlying enhanced glutamatergic synaptic input to PVN presympathetic neurons in hypertension. In this review article, we summarize recent findings on changes in inotropic and metabotropic glutamate receptors, at both presynaptic and postsynaptic sites, responsible for increased glutamatergic input to PVN presympathetic neurons in hypertension. Particular emphasis is placed on the role of protein kinases and phosphatases in the potentiated activity of synaptic NMDA receptors in the PVN in hypertension. New findings about glutamatergic synaptic plasticity in the PVN not only improve the understanding of molecular mechanisms involved in heightened activity of the sympathetic nervous system but also suggest new therapeutic targets for treating drug-resistant, neurogenic hypertension.