Role of the organum vasculosum of the lamina terminalis for the chronic cardiovascular effects produced by endogenous and exogenous ANG II in conscious rats

Vieira, Alexandre Antonio; Nahey, David; Collister, John P.

doi:10.1152/ajpregu.00034.2010

Cited by 29 publications

(45 citation statements)

References 35 publications

(44 reference statements)

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“…It is likely that they have a role in the centrally mediated pressor effect (Vieira et al, 2010) and sodium appetite caused by circulating angiotensin II (Simpson, 1981;Fitts et al, 2004).…”

Section: Neuroendocrine Autonomic and Neuroimmune Functionsmentioning

confidence: 99%

Circumventricular Organs

Oldfield

2015

The Rat Nervous System

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Section: Neuroendocrine Autonomic and Neuroimmune Functionsmentioning

confidence: 99%

Circumventricular Organs

Oldfield

2015

The Rat Nervous System

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“…If leakage of drug infused in the PVN into the cerebrospinal fluid played a major role, one would expect the opposite pattern. However, considering that nuclei in the LT play an important role in initiating the central responses to circulating Ang II, 20,38 one would expect that intracerebroventricular infusion of kynurenate at the PVN dose would cause some blockade in the LT, and some decrease in BP.…”

Section: Limitationsmentioning

confidence: 99%

Central Mineralocorticoid Receptors and the Role of Angiotensin II and Glutamate in the Paraventricular Nucleus of Rats With Angiotensin II–Induced Hypertension

Gabor

Leenen

2013

Hypertension

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A chronic increase in circulating angiotensin II (Ang II) increases neuronal activation in hypothalamic nuclei, such as the paraventricular nucleus (PVN), 1,2 and causes progressive hypertension, 2,3 presumably by increasing sympathetic activity. [4][5][6] A central neuromodulatory pathway involving aldosterone-endogenous ouabain (EO) seems to play a critical role in these responses to Ang II. 2,7 Chronic subcutaneous infusion of Ang II increases plasma and hypothalamic aldosterone content. 2 Intracerebroventricular infusion of an aldosterone synthase (AS) inhibitor prevents increase in hypothalamic, but not in plasma aldosterone, and intracerebroventricular infusion of an AS inhibitor or a mineralocortoicod receptor (MR) blocker markedly attenuate the neuronal activation in the PVN.2 Intracerebroventricular infusion of an AS inhibitor, 2 MR blocker, 2,7 EO-binding antibody Fab fragments (Digibind), 2 or an angiotensin type 1 (AT 1 )-receptor blocker 8 largely prevents the Ang II-induced hypertension. These findings suggest that a chronic increase in circulating Ang II increases local hypothalamic aldosterone production, and activates an MR-EO pathway in the brain, which is essential for the Ang II-induced hypertension.Several models of chronic sympathetic hyperactivity are associated with an increase in glutamate receptor and AT 1 -receptor activation in the PVN. A glutamate or AT 1 -receptor blocker in the PVN decreases sympathetic nerve activity, blood pressure (BP), and heart rate (HR) in rats with chronic heart failure 9,10 and in spontaneously hypertensive rats. 11 Glutamate and AT 1 -receptor blockers in the PVN decrease BP in waterdeprived rats 12 and in Dahl S rats on high-salt diet. 13 In Dahl S rats on a high-salt diet, at the peak BP decrease by a glutamate receptor blocker, an AT 1 -receptor blocker in the PVN does not further decrease BP. 13 These findings suggest that the effects of increased AT 1 -receptor activation in the PVN of hypertensive Dahl S rats are fully mediated by local glutamate release. Consistent with these findings, Ang II increases glutamatergic signaling in the PVN, either by increasing glutamate release from interneurons, 14,15 or by decreasing gamma-amino butyric acid (GABA)-mediated inhibition of the PVN. 16,17 No studies have yet evaluated the role of the central aldosterone neuromodulatory pathway in Ang II and glutamate receptor activation in the PVN of hypertensive rats. We hypothesized Abstract-A chronic increase in circulating angiotensin II (Ang II) activates an aldosterone-mineralocorticoid receptorouabain neuromodulatory pathway in the brain that increases neuronal activation in hypothalamic nuclei, such as the paraventricular nucleus (PVN) and causes progressive hypertension. Several models of chronic sympathetic hyperactivity are associated with an increase in AT 1 and glutamate receptor activation in the PVN. The current study evaluated whether increased angiotensin type 1 (AT 1 ) and glutamate receptor-dependent signaling in the PVN contributes to the mainten...

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“…Thus, circulating Ang II may stimulate nuclei outside the BBB and lead to direct activation of the PVN and SON, causing the initial pressor response; in addition, it can cause sustained activation of the PVN via activation of aldosterone-"ouabain"-dependent amplifying mechanisms, thereby producing sustained sympathetic hyperactivity and progressive hypertension. Both the SFO [51,53] and the organum vasculosum of the lamina terminalis (OVLT) [54] may be the primary targets of Ang II.…”

Section: Activation By Sodium In Cerebrospinal Fluidmentioning

confidence: 99%

Mineralocorticoid Actions in the Brain and Hypertension

Huang

Leenen

2011

Curr Hypertens Rep

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Mineralocorticoid receptors (MR) and epithelial sodium channels (ENaC) in the brain mediate central aldosterone-induced sympathetic hyperactivity and hypertension. Enzymes for biosynthesis of aldosterone are present in the brain, and aldosterone can be produced locally in the brain. Hypothalamic aldosterone levels increase in Dahl salt-sensitive rats on high-salt diet, and in Wistar rats with chronic central infusion of sodium-rich artificial cerebrospinal fluid (CSF) or with subcutaneous infusion of angiotensin II. Functional studies using antagonists of MR, ENaC, and ouabain-like compounds ("ouabain"), as well as specific aldosterone synthase inhibitors, suggest that an increase in local synthesis of aldosterone via MR and ENaC in the brain increases "ouabain" and thereby causes enhanced AT(1) receptor stimulation, leading to sympathoexcitation and hypertension. An increase in CSF sodium or an increase in angiotensinergic output from circumventricular organs such as the subfornical organ projecting to hypothalamic nuclei may increase local production of aldosterone and "ouabain" in magnocellular neurons in the supraoptic nucleus and paraventricular nucleus. This aldosterone-"ouabain" neuromodulatory mechanism appears to play a major role in salt-induced or angiotensin II-induced hypertension.

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Role of the organum vasculosum of the lamina terminalis for the chronic cardiovascular effects produced by endogenous and exogenous ANG II in conscious rats

Cited by 29 publications

References 35 publications

Circumventricular Organs

Circumventricular Organs

Central Mineralocorticoid Receptors and the Role of Angiotensin II and Glutamate in the Paraventricular Nucleus of Rats With Angiotensin II–Induced Hypertension

Mineralocorticoid Actions in the Brain and Hypertension

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