Local circuitry regulates the excitability of rat neurohypophysial neurones.

The importance of angiotensin II (AII) and glutamate has long since been recognized in neuroendocrine regulation. However, the mechanisms by which AII and glutamate modulate the excitability of the paraventricular nucleus (PVN) have largely remained a mystery until recently. It is now apparent that AII and glutamate are potent stimulators of both magnocellular and parvocellular neurones in the rat PVN. While glutamate, the predominant excitatory neurotransmitter in the CNS, ubiquitously excites PVN neurones, AII appears to mediate excitability of the PVN by both direct and indirect mechanisms. Interestingly, both of these neurotransmitters, upon exciting the PVN, activate an inhibitory feedback system, which is capable of diminishing the initial stimulus. Physiologically, this moderates the output signals from the PVN, and probably also regulates neuropeptide release from the neurohypophysis. The importance of this negative-feedback loop is evident in the pathophysiological implications of a disruption in the system. Evidence suggests that a breakdown in this system may be responsible in part for the onset and maintenance of both congestive heart failure and hypertension. Future studies will continue to characterize both the actions of glutamate and AII in the PVN, and to further elucidate the mechanisms which control the excitability of the PVN.