Long‐term Regulation of Arterial Blood Pressure by Hypothalamic Nuclei: Some Critical Questions

Abstract

1. The long-term level of arterial pressure is dependent on the relationship between arterial pressure and the urinary output of salt and water, which, in turn, is affected by a number of factors, including renal sympathetic nerve activity (RSNA). In the present brief review, we consider the mechanisms within the brain that can influence RSNA, focusing particularly on hypothalamic mechanisms. 2. The paraventricular nucleus (PVN) in the hypothalamus has major direct and indirect connections with the sympathetic outflow and there is now considerable evidence that tonic activation of the PVN sympathetic pathway contributes to the sustained increased level of RSNA that occurs in conditions such as heart failure and neurogenic hypertension. The tonic activity of PVN sympathetic neurons, in turn, depends upon the balance of excitatory and inhibitory inputs. A number of neurotransmitters and neuromodulators are involved in these tonic excitatory and inhibitory effects, including glutamate, GABA, angiotensin II and nitric oxide. 3. The dorsomedial hypothalamic nucleus (DMH) also exerts a powerful influence over sympathetic activity, including RSNA, via synapses with sympathetic nuclei in the medulla and, possibly, also other brainstem regions. The DMH sympathetic pathway is an important component of the phasic sympathoexcitatory responses associated with acute stress, but there is no evidence that it is an important component of the central pathways that produce long-term changes in arterial pressure. Nevertheless, it is possible that repeated episodic activation of this pathway could lead to vascular hypertrophy and, thus, sustained changes in vascular resistance and arterial pressure. 4. Recent studies have reactivated the old debate concerning the possible role of the baroreceptor reflex in the long-term regulation of sympathetic activity. Therefore, central resetting of the baroreceptor-sympathetic reflex may be an important component of the mechanisms causing sustained changes in RSNA. However, little is known about the cellular mechanisms that could cause such resetting.

TNF-.ALPHA. in Hypothalamic Paraventricular Nucleus Contributes to Sympathoexcitation in Heart Failure by Modulating AT1 Receptor and Neurotransmitters

“…Measurements at 4-weeks RV/BW (mg/g) Lung/BW (mg/g) thetic activity, indicating a role for the central nervous system RAS in sympathoexcitation in HF (Zhang, Francis et al 2002;Dampney et al 2005). Findings from our laboratory and others indicate that cytokines interact with RAS both in the central and peripheral nervous systems (Guggilam et al 2008;Kang et al 2008aKang et al , 2008bKang et al , 2009a.…”

Ghrelin promotes hepatic lipogenesis by activation of mTOR-PPARγ signaling pathway

“…control of adiposity (14) and modulation of blood pressure (15), targeting the hypothalamic ghrelin receptor/GHSR1a for treatment of metabolic dysfunction without systemic side effects is challenging. Recent studies suggest alternative pathways for lipid metabolism involving peripheral actions of ghrelin.…”

Cranial Visceral Afferent Pathways through the Nucleus of the Solitary Tract to Caudal Ventrolateral Medulla or Paraventricular Hypothalamus: Target-Specific Synaptic Reliability and Convergence Patterns

“…CVLM contains the critical intermediary neurons in the baroreflex pathway that mediate baroreceptorinitiated sympathoinhibition of sympathetic neurons within the rostral ventrolateral medulla (Aicher et al, 1995). PVN receives dense inputs from NTS (Ruggiero et al, 1994) that impact a mix of reflex outcomes from PVN that integrate neuroendocrine, stress, and homeostatic responses (Chen and Toney, 2003;Herman et al, 2003;Dampney et al, 2005;Guyenet, 2006). Neurons in these two regions display qualitatively different responses to baroreceptor afferent activation.…”