Neurochemistry of the paraventricular nucleus of the hypothalamus: implications for cardiovascular regulation.

The paraventricular nucleus of the hypothalamus (PVN) is an important site for autonomic and endocrine homeostasis. The PVN integrates specific afferent stimuli to produce an appropriate differential sympathetic output. The neural circuitry and some of the neurochemical substrates within this circuitry are discussed. The PVN has at least three neural circuits to alter sympathetic activity and cardiovascular regulation. These pathways innervate the vasculature and organs such as the heart, kidney and adrenal medulla. The basal level of sympathetic tone at any given time is dependent upon excitatory and inhibitory inputs. Under normal circumstances the sympathetic nervous system is tonically inhibited. This inhibition is dependent upon GABA and nitric oxide such that nitric oxide potentiates local GABAergic synaptic inputs onto the neurones in the PVN. Excitatory neurotransmitters such as glutamate and angiotensin II modify the tonic inhibitory activity. The neurotransmitters oxytocin, vasopressin and dopamine have been shown to affect cardiovascular function. These neurotransmitters are found in neurones of the PVN and within the spinal cord. Oxytocin and vasopressin terminal fibres are closely associated with sympathetic preganglionic neurones (SPNs). Sympathetic preganglionic neurones have been shown to express receptors for oxytocin, vasopressin and dopamine. Oxytocin causes cardioacceleratory and pressor effects that are greatest in the upper thoracic cord while vasopressin cause these effects but more significant in the lower thoracic cord. Dopaminergic effects on the cardiovascular system include inhibitory or excitatory actions attributed to a direct PVN influence or via interneuronal connections to sympathetic preganglionic neurones.