Neurochemistry of the paraventricular nucleus of the hypothalamus: Implications for cardiovascular regulation

Pyner, Susan

doi:10.1016/j.jchemneu.2009.03.005

Cited by 147 publications

(168 citation statements)

References 162 publications

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“…We demonstrated that the chronic intracerebroventricular infusion of a synthetic selective GR agonist did not alter the blood pressure in a normotensive rat, but that the concomitant intracerebroventricular infusion of equimolar and twice molar concentrations of corticosterone with aldosterone inhibited the intracerebroventricular aldosterone hypertension in a dose-related fashion (35,50). Our present results suggest that the higher concentrations of corticosterone produced by the infusion acted indirectly upon preautonomic neurons to decrease their excitability, perhaps through GABAergic parvocellular neurons that express GR, as discussed above (15,87). In addition, GR activation in neurons of the PVN was shown to dampen the excitability of other PVN neurons through the endocannabinoid system (101).…”

Section: Discussionsupporting

confidence: 50%

Expression of mineralocorticoid and glucocorticoid receptors in preautonomic neurons of the rat paraventricular nucleus

Chen

Gómez-Sánchez

Penman

et al. 2014

American Journal of Physiology-Regulatory, Integrative and Comp

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Activation of mineralocorticoid receptors (MR) of the hypothalamic paraventricular nucleus (PVN) increases sympathetic excitation. To determine whether MR and glucocorticoid receptors (GR) are expressed in preautonomic neurons of the PVN and how they relate to endogenous aldosterone levels in healthy rats, retrograde tracer was injected into the intermediolateral cell column at T4 to identify preautonomic neurons in the PVN. Expression of MR, GR, 11-␤ hydroxysteroid dehydrogenase1 and 2 (11␤-HSD1, 2), and hexose-6-phosphate dehydrogenase (H6PD) required for 11␤-HSD1 reductase activity was assessed by immunohistochemistry. RT-PCR and Western blot analysis were used to determine MR gene and protein expression. Most preautonomic neurons were in the caudal mediocellular region of PVN, and most expressed MR; none expressed GR. 11␤-HSD1, but not 11␤-HSD2 nor H6PD immunoreactivity, was detected in the PVN. In rats with chronic low or high sodium intakes, the low-sodium diet was associated with significantly higher plasma aldosterone, MR mRNA and protein expression, and c-Fos immunoreactivity within labeled preautonomic neurons. Plasma corticosterone and sodium and expression of tonicity-responsive enhancer binding protein in the PVN did not differ between groups, suggesting osmotic adaptation to the altered sodium intake. These results suggest that MR within preautonomic neurons in the PVN directly participate in the regulation of sympathetic nervous system drive, and aldosterone may be a relevant ligand for MR in preautonomic neurons of the PVN under physiological conditions. Dehydrogenase activity of 11␤-HSD1 occurs in the absence of H6PD, which regenerates NADP ϩ from NADPH and may increase MR gene expression under physiological conditions. mineralocorticoid receptor; aldosterone; sympathetic nervous system; preautonomic neuron; paraventricular nucleus; glucocorticoid receptor; 11-␤ hydroxysteroid dehydrogenase; sodium THE RENIN-ANGIOTENSIN-ALDOSTERONE system (RAAS) and sympathetic nervous system (SNS) interact to maintain fluid, electrolyte, and hemodynamic homeostasis essential for terrestrial life where sodium intake is often limited. Both the RAAS and SNS are activated by a lowering sodium intake, adaptive mechanisms ensuring adequate blood pressure (17,51,52,60,64,104). The paraventricular nucleus (PVN), and the SNS were shown by ablation studies to have a crucial role in mineralocorticoid-salt excess models of hypertension (6, 58). Chronic systemic aldosterone excess, as well as the intracerebroventricular infusion of aldosterone administered at concentrations too low to be effective when infused systemically, increase blood pressure and SNS activity (35,61). In both models, the hypertension and sympathetic activation are prevented by the intracerebroventricular infusion of mineralocorticoid receptor (MR) antagonists at doses lower than the effective dose infused peripherally (35,39,61). Xue et al. (108) reproduced these pharmacological results with the intracerebroventricular infusion of MR siRNA (108).The ...

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Section: Discussionsupporting

confidence: 50%

Expression of mineralocorticoid and glucocorticoid receptors in preautonomic neurons of the rat paraventricular nucleus

Chen

Gómez-Sánchez

Penman

et al. 2014

American Journal of Physiology-Regulatory, Integrative and Comp

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“…Presympathetic neurons in the PVN send monoand poly-synaptic projections to the sympathetic preganglionic neurons residing in the IML of the spinal cord (55). The released acetylcholine from the sympathetic pre ganglionic neurons located in T7-9 (56) activates the adrenal chromaffin cells, thereby evoking the secretion of catecholamines from the adrenal medulla.…”

Section: V) A)mentioning

confidence: 99%

Stimulatory and Inhibitory Roles of Brain 2-Arachidonoylglycerol in Bombesin-Induced Central Activation of Adrenomedullary Outflow in Rats

2013

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Abstract. 2-Arachidonoylglycerol (2-AG) is recognized as a potent endocannabinoid, which reduces synaptic transmission through cannabinoid CB 1 receptors, and is hydrolyzed by monoacylglycerol lipase (MGL) to arachidonic acid (AA), a cyclooxygenase substrate. We already reported that centrally administered MGL and cyclooxygenase inhibitors each reduced the intracerebroventricularly (i.c.v.) administered bombesin-induced secretion of adrenal catecholamines, while a centrally administered CB 1 -antagonist potentiated the response, indirectly suggesting bidirectional roles of brain 2-AG (stimulatory and inhibitory roles) in the bombesin-induced response. In the present study, we separately examined these bidirectional roles using 2-AG and 2-AG ether (2-AG-E) (stable 2-AG analog for MGL) in rats.

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“…The PVN synthesizes over 30 different neurotransmitters (Pyner, 2009), including GABA, NO and glutamate produced by neurons involved in tonic inhibition of pre-ganglionic sympathetic neurons under baseline physiological conditions, as well as in OT-, and dopamineproducing neurons that selectively modulate this tonic inhibitory signal (Pyner, 2009). …”

Section: Discussionmentioning

confidence: 99%

Over-expression of V1A receptors in PVN modulates autonomic cardiovascular control

Lozić

Tasić

Martin

et al. 2016

Pharmacological Research

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The hypothalamic paraventricular nucleus (PVN) is a key integrative site for the neuroendocrine control of the circulation and of the stress response. It is also a major source of the neuropeptide hormone vasopressin (VP), and co-expresses V1a receptors (V1aR). We thus sought to investigate the role of V1aR in PVN in cardiovascular control in response to stress.Experiments were performed in male Wistar rats equipped with radiotelemetric device. The right PVN was transfected with adenoviral vectors (Ads) engineered to over-express V1aR along with an enhanced green fluorescent protein (eGFP) tag. Control groups were PVN transfected with Ads expressing eGFP alone, or wild-type rats (Wt). Rats were recorded with and without selective blockade of V1aR (V1aRX) in PVN under both baseline and stressed conditions. Blood pressure (BP), heart rate (HR), their short-term variabilities, and baroreflex sensitivity (BRS) were evaluated using spectral analysis and the sequence method, respectively. Under baseline physiological conditions,V1aR rats exhibited reduced BRS and a marked increase of BP and HR variability during exposure to stress. These effects were all prevented by V1aRX pretreatment. In Wt rats, V1aRX did not modify cardiovascular parameters under baseline conditions, and prevented BP variability increase by stress.However, V1aRX pretreatment did not modify baroreflex desensitization by stress in either rat strain. It follows that increased expression of V1aR in PVN influences autonomic cardiovascular regulation and demarcates vulnerability to stress. We thus suggest a possible role of hypothalamic V1aR in cardiovascular pathology. KeywordsVasopressin, V1a receptor, paraventricular nucleus, adenoviral vector, baroreflex, blood pressure variability, heart rate variability Abbreviations BRS, baroreflex sensitivity; VLF, very low frequency short-term variability; LF, low frequency short-term variability; HF, high frequency short-term variability; VP, vasopressin;OT, oxytocin; OTR, oxytocin receptor; V1aR, vasopressin V1a receptor; V1bR, vasopressin V1b receptor; V2R, vasopressin V2 receptor; V1aRX, vasopressin V1a receptor antagonist, PVN, paraventricular nucleus; NTS, nucleus of the solitary tract; RVLM; rostroventrolateral medulla; IML, intermediolateral column of the spinal cord.

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Neurochemistry of the paraventricular nucleus of the hypothalamus: Implications for cardiovascular regulation

Cited by 147 publications

References 162 publications

Expression of mineralocorticoid and glucocorticoid receptors in preautonomic neurons of the rat paraventricular nucleus

Expression of mineralocorticoid and glucocorticoid receptors in preautonomic neurons of the rat paraventricular nucleus

Stimulatory and Inhibitory Roles of Brain 2-Arachidonoylglycerol in Bombesin-Induced Central Activation of Adrenomedullary Outflow in Rats

Over-expression of V1A receptors in PVN modulates autonomic cardiovascular control

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