Vasopressin Acts in the Subfornical Organ to Decrease Blood Pressure

Smith, Pauline; Ferguson, Alastair V.

doi:10.1159/000127230

Cited by 29 publications

(26 citation statements)

References 18 publications

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“…Of particular interest is the subfornical projection to the hypothalamic paraventricular and supraoptic nuclei which may influence directly the neuroendocrine activity of vasopressinergic neurons, as well as modify autonomic output through descending paraventricular projections to the spinal cord. The sensitivity of subfornical neurons to circulating AVP suggests that the subfornical organ represents an essential structure in a feedback loop through which circulating AVP influences cardiovascular control [26]. Neurons of the area postrema connect to the adjacent nucleus of the solitary tract, a structure involved in baroreflex and cardiovascular regulation [27, 28], control of fluid homeostasis, food intake and development of conditioned taste aversions associated with nausea [29].…”

Section: Discussionmentioning

confidence: 99%

Binding of the Non-Peptide Vasopressin V<sub>1a</sub> Receptor Antagonist SR-49059 in the Rat Brain: An in vitro and in vivo Autoradiographic Study

Tribollet¹,

Raufaste

Maffrand

et al. 1999

Neuroendocrinology

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A potent non-peptide vasopressin (AVP) antagonist, SR-49059, displaying high stability and selective affinity for the V_1a AVP receptor subtype, has recently been described. The objective of this study was to assess the binding properties and the penetrability of this compound in the rat brain. Both in vitro and in vivo binding autoradiography experiments were performed. In all studies, the liver was used as a reference V_1a tissue. In vitro labelling of rat brain sections with [³H]SR-49059 was similar to that previously detected with [³H]AVP, which confirms that the majority of central AVP binding sites are V_1a sites similar to peripheral V_1a receptors. As expected, intense specific labelling occurred mainly in the lateral septum, the fundus striatum, the hypothalamic stigmoid nucleus and the area postrema-nucleus of the solitary tract complex. In vivo binding autoradiography showed that [³H]SR-49059 injected intravenously did not enter the brain parenchyma. Specific labelling was however clearly detectable in brain regions with permeable hematoencephalic barrier, the choroid plexus and other circumventricular organs expressing V_1a receptors, namely the subfornical organ, the pineal gland and the area postrema. The specificity of [³H]SR-49059 binding in the latter structures was confirmed by the fact that labelling was prevented by pretreatment of animals with high doses of nonradioactive SR-49059. In conclusion, our study shows that [³H]SR-49059 is a suitable probe to investigate V_1a receptors in the rat brain. We also demonstrate that although this compound is not able to enter the brain tissue from the peripheral circulation, it does bind specifically to regions devoid of blood-brain barrier and known to be involved in autonomic regulations.

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Section: Discussionmentioning

confidence: 99%

Binding of the Non-Peptide Vasopressin V<sub>1a</sub> Receptor Antagonist SR-49059 in the Rat Brain: An in vitro and in vivo Autoradiographic Study

Tribollet¹,

Raufaste

Maffrand

et al. 1999

Neuroendocrinology

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“…Other regulatory peptides known for effects on the cardiovascular system that have been shown to influence blood pressure as a result of actions in the SFO include vasopressin (116,137) and atrial natriuretic peptide (105). In addition, the reproductive hormone, relaxin (82), the orexigenic and arousal neuropeptide, orexin (118), and the adipose tissue-derived hormone, leptin (P. Smith and A. Ferguson, unpublished observation) have also been shown to influence blood pressure when microinjected into the SFO.…”

Section: Anatomical Features Of the Sfomentioning

confidence: 99%

Circulating signals as critical regulators of autonomic state—central roles for the subfornical organ

Smith

Ferguson

2010

American Journal of Physiology-Regulatory, Integrative and Comp

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To maintain homeostasis autonomic control centers in the hypothalamus and medulla must respond appropriately to both external and internal stimuli. Although protected behind the blood-brain barrier, neurons in these autonomic control centers are known to be influenced by changing levels of important signaling molecules in the systemic circulation (e.g., osmolarity, glucose concentrations, and regulatory peptides). The subfornical organ belongs to a group of specialized central nervous system structures, the circumventricular organs, which are characterized by the lack of the normal blood-brain barrier, such that circulating lipophobic substances may act on neurons within this region and via well-documented efferent neural projections to hypothalamic autonomic control centers, influence autonomic function. This review focuses on the role of the subfornical organ in sensing peripheral signals and transmitting this information to autonomic control centers in the hypothalamus.

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“…They play important roles in sensing circulating signals from the periphery and sending such information to control centres behind the blood-brain barrier responsible for the regulation of autonomic responses [25]. The SFO has been shown to play critical roles in the control of blood pressure by integrating signals from a wide range of circulating neuropeptides including vasopressin [26], [27], orexin [28], apelin [29], angiotensin II [30], [31], atrial natriuretic peptide [32], and leptin [33]. It has also recently been shown that both NAPDH oxidases and superoxide both play a critical role in the SFO regarding angiotensin II induced hypertension, with site specific knockdown in SFO reducing hypertension induced by angiotensin II infusion [34], [35].…”

Section: Introductionmentioning

confidence: 99%

Hydrogen Sulfide Regulates Cardiovascular Function by Influencing the Excitability of Subfornical Organ Neurons

2014

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Hydrogen sulfide (H2S), a gasotransmitter endogenously found in the central nervous system, has recently been suggested to act as a signalling molecule in the brain having beneficial effects on cardiovascular function. This study was thus undertaken to investigate the effect of NaHS (an H2S donor) in the subfornical organ (SFO), a central nervous system site important to blood pressure regulation. We used male Sprague-Dawley rats for both in vivo and in vitro experiments. We first used RT-PCR to confirm our previous microarray analyses showing that mRNAs for the enzymes required to produce H2S are expressed in the SFO. We then used microinjection techniques to investigate the physiological effects of NaHS in SFO, and found that NaHS microinjection (5 nmol) significantly increased blood pressure (mean AUC = 853.5±105.7 mmHg*s, n = 5). Further, we used patch-clamp electrophysiology and found that 97.8% (88 of 90) of neurons depolarized in response to NaHS. This response was found to be concentration dependent with an EC50 of 35.6 µM. Coupled with the depolarized membrane potential, we observed an overall increase in neuronal excitability using an analysis of rheobase and action potential firing patterns. This study has provided the first evidence of NaHS and thus H2S actions and their cellular correlates in SFO, implicating this brain area as a site where H2S may act to control blood pressure.

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Vasopressin Acts in the Subfornical Organ to Decrease Blood Pressure

Cited by 29 publications

References 18 publications

Binding of the Non-Peptide Vasopressin V<sub>1a</sub> Receptor Antagonist SR-49059 in the Rat Brain: An in vitro and in vivo Autoradiographic Study

Binding of the Non-Peptide Vasopressin V<sub>1a</sub> Receptor Antagonist SR-49059 in the Rat Brain: An in vitro and in vivo Autoradiographic Study

Circulating signals as critical regulators of autonomic state—central roles for the subfornical organ

Hydrogen Sulfide Regulates Cardiovascular Function by Influencing the Excitability of Subfornical Organ Neurons

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