Role of the hypothalamic PVN in the regulation of renal sympathetic nerve activity and blood flow during hyperthermia and in heart failure

Abstract

The hypothalamic paraventricular nucleus is a key integrative area in the brain involved in influencing sympathetic nerve activity and in the release of hormones or releasing factors that contribute to regulating body fluid homeostasis and endocrine function. The endocrine and hormonal regulatory function of the paraventricular nucleus is well studied, but the regulation of sympathetic nerve activity and blood flow by this region is less clear. Here we review the critical role of the paraventricular nucleus in regulating renal blood blow during hyperthermia and the evidence pointing to an important pathophysiological role of the paraventricular nucleus in the elevated renal sympathetic nerve activity that is a characteristic of heart failure.

Fig. 1.

Percent changes in mesenteric (n = 11) and renal (n = 11) blood flows and vascular conductances in response to elevations in body core temperature in urethane-anesthetized rats. Separate animals were used for the renal and mesenteric studies. The body core temperature was raised at a rate of ∼0.1°C every 2 min by using a water jacket as described previously (9, 11).

Fig. 2.

Schema summarizing the effect of raising body core temperature and activation of neurons in the hypothalamic paraventricular nucleus (PVN) that include neurons projecting to the sympathetic preganglionic motor neurons (SPN) in the spinal cord or to the pressor region of rostral ventrolateral medulla (RVLM). The result is an increase in renal sympathetic nerve activity (RSNA) and a reduction in renal blood flow.

Fig. 3.

Schema summarizing the potential mechanisms that contribute to an increase in neuronal activity in the hypothalamic PVN and an elevation in RSNA in heart failure. The actions of excitatory neurotransmitters such as ANG II and glutamate (Glut) are enhanced while the inhibitory influences of GABA and nitric oxide (NO) are reduced. There is also an increase in proinflammatory cytrokines such as TNF-α and IL-1β. The actions of these may involve PGE₂, the transcription factor NF-κB, and reactive oxygen species (ROS). These can act to further promote the inflammatory process. PGE₂ may also contribute to the reduced GABA function. ANG II may act directly to increase neuronal activity as well as acting to increase proinflammatory cytokines.