Long-term regulation of arterial blood pressure by hypothalamic nuclei: Some critical questions

R. A L Dampney*, J. Horiuchi, S. Killinger, M. J. Sheriff, P. S P Tan, L. M. McDowall

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

175 Citations (Scopus)


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. 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. 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. 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.

Original languageEnglish
Pages (from-to)419-425
Number of pages7
JournalClinical and Experimental Pharmacology and Physiology
Issue number5-6
Publication statusPublished - May 2005
Externally publishedYes


  • Angiotensin II
  • Baroreceptor reflex
  • Blood pressure regulation
  • Dorsomedial hypothalamic nucleus
  • Hypertension
  • Hypothalamic paraventricular nucleus
  • Nitric oxide
  • Renal sympathetic nerve activity


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