PVH and heart failure

The topic of this paper examines cellular and molecular mechanisms in the PVH in the pathophysiological state of heart failure. A key aspect of heart failure is the inability to regulate the sympathetic nervous system. The PVH is a key regulatory brain region responsible for sympathetic regulation and ultimately arterial pressure. Afferent projections from the cardiovascular system to the NTS initiate cardiovascular regulation through projects to the PVH and the RVLM. The PVH and RVLM subsequently adjust their sympathetic response from the NTS to regulate homeostasis. Furthermore, the PVH sends efferent projections to the sympathetic preganglionic neurons of the RVLM and IML to regulate sympathetic tone. The IML is critical in the maintenance of arterial pressure since it regulates sympathetic preganglionic neurons of the entire body.

The PVH alone is an important regulator of arterial pressure. The three important subsets of neurons within the PVH are the magnocellular, the parvocellular neuroendocrine, and parvocellular pre-autonomic neurons. The magnocellular neurons synthesize and secrete vasopressin and oxytocin which are released into circulation through the posterior pituitary. The parvocellular neuroendocrine hormones release GHRH to the anterior pituitary via the hypophyseal portal vessels. Finally, the parvocellular pre autonomic neurons regulate sympathetic nerve activity. An important aspect of the PVH is that the parvocellular pre autonomic neurons project reciprocally to the NTS as well as the RVLM and IML to regulate arterial pressure.

 A critical discovery by Pyner, demonstrated at least 4 pathways from the NTS project target PVH neurons: spinally projecting neurons, nNOS-magnocellular neurons, GABA interneurons, and nNOS containing interneurons bordering the PVH. This discovering is important in being able to assess sensory inputs to the NTS with the PVH.

The PVH is under tonic inhibitory control via NO mediated GABA inhibition. Excitation of the PVH requires NMDA mediated glutamate driven activation in the PVN. A major finding implicated the NDMA glutamate stimulation in heart failure since no increases in blood pressure were discovered during tonic glutamate administration. However, when sympathetic nerve activity is enhanced in conditions of heart failure, administration of a NMDA antagonist decreased sympathetic nerve activity. This raised the question of why and how this happens if tonic increases in glutamate did not give rise to sympathetic nerve activity in normal conditions. Increasing evidence suggests angiontensin 2 and downregulation of nNOS an enzyme responsible for NO generation.

The paper elaborates on the PVH and finds new projections to the PVH from the NTS as well as examines the effects that heart failure has on PVH. However, information has not been discovered yet to determine a viable drug target for regulating many of these pathways in heart failure.