GABA in the paraventricular nucleus tonically suppresses baroreflex function: alterations during pregnancy

Page, Mollie; Cassaglia, Priscila A.; Brooks, Virginia L.

doi:10.1152/ajpregu.00736.2010

Cited by 17 publications

(23 citation statements)

References 34 publications

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“…A major contributor to this increased SNA may be reduced tonic inhibition of PVN presympathetic neurons. In addition to the previously reported decreases in GABAergic 13, 14 and nNOS-mediated 15 SNA suppression, our data suggest that tonic PVN NPY inhibition of SNA is also lessened. First, similar to the mouse, 18 we found that PVN NPY expression is decreased in pregnant rats.…”

Section: Discussionsupporting

confidence: 79%

“…Second, PVN NPY-induced sympathoinhibition was preserved, but the normal sympathoexcitatory response to PVN NPY Y1R blockade was abolished in pregnant rats. The failure of NPY1× to increase SNA in pregnant rats cannot be because the elevated basal SNA has reached a maximal level, since baroreceptor unloading 12, 14 and PVN nanoinjection of the GABA A antagonist, bicuculline, 13, 14 can both increase SNA further in pregnant rats. Nevertheless, our ihc data appear to conflict with studies showing that the expression of NPY [and the co-expressed agouti-related peptide (AgRP)] in the ArcN, one major source of PVN NPY inputs, is increased or unchanged during late pregnancy, 28-30 and that PVN NPY Y1R may be elevated.…”

Section: Discussionmentioning

confidence: 99%

“…In contrast, while the paraventricular nucleus of the hypothalamus (PVN) normally contributes little to basal sympathetic tone, indirect evidence suggests that the PVN may underlie basal sympathoexcitation in pregnancy. More specifically, sympathoinhibitory influences in the PVN, including the considerable tonic GABAergic restraint 13, 14 and the expression and activity of neuronal nitric oxide synthase (nNOS), 15, 16 are decreased. However, whether this decreased inhibition translates into higher tonic support of basal SNA is unknown.…”

Section: Introductionmentioning

confidence: 99%

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Hypothalamic Paraventricular and Arcuate Nuclei Contribute to Elevated Sympathetic Nerve Activity in Pregnant Rats

et al. 2015

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Pregnancy increases sympathetic nerve activity, but the mechanisms are unknown. Here, we investigated the contributions of the hypothalamic paraventricular and arcuate nuclei in α-chloralose-anesthetized pregnant and nonpregnant rats. Baseline arterial pressure was lower, and heart rate, lumbar sympathetic activity and splanchnic sympathetic nerve activity were higher in pregnant compared to nonpregnant rats. Inhibition of the paraventricular nucleus via bilateral muscimol nanoinjections decreased arterial pressure more in pregnant than nonpregnant rats, and decreased heart rate and lumbar sympathetic nerve activity only in pregnant rats. Similarly, following arcuate muscimol nanoninjections, the decreases in arterial pressure, heart rate, and lumbar, renal, and splanchnic sympathetic nerve activities, were greater in pregnant than nonpregnant rats. Major arcuate neuronal groups that project to the paraventricular nucleus express inhibitory Neuropeptide Y and excitatory α-melanocyte stimulating hormone. Inhibition of paraventricular melanocortin 3/4 receptors with SHU9119 also decreased arterial pressure, heart rate, and lumbar sympathetic nerve activity in pregnant, but not nonpregnant rats. Conversely, paraventricular nucleus Neuropeptide Y expression was reduced in pregnant animals, and while blockade of paraventricular Neuropeptide Y Y1 receptors increased arterial pressure, heart rate, and lumbar sympathetic activity in nonpregnant rats, it had no effects in pregnant rats. Yet, the sympathoinhibitory, depressor and bradycardic effects of Neuropeptide Y nanoinjections were similar between groups. In conclusion, the paraventricular and arcuate nuclei contribute to increased basal sympathetic nerve activity during pregnancy, likely due in part to decreased tonic Neuropeptide Y inhibition and increased tonic α-melanocyte stimulating hormone excitation of presympathetic neurons in the paraventricular nucleus.

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Section: Discussionsupporting

confidence: 79%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Hypothalamic Paraventricular and Arcuate Nuclei Contribute to Elevated Sympathetic Nerve Activity in Pregnant Rats

et al. 2015

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“…Previous work from others investigating the regulatory role of GABA inputs in the PVN on baroreflex control using pharmacologic techniques (intravenous infusion of nitroprusside and phenylephrine) documented an increase in baroreflex sensitivity after GABAa inhibition with bicuculline, and this was specifically due to changes in baroreflex sensitivity during the hypotensive state induced by the intravenous infusion of nitroprusside (32). Also, intravenous nitroprusside may change nitric oxide levels, potentially affecting GABA mechanisms.…”

Section: Discussionmentioning

confidence: 96%

Exercise training normalizes the blunted central component of the baroreflex in rats with heart failure: role of the PVN

Patel

Salgado

Liu

et al. 2013

American Journal of Physiology-Heart and Circulatory Physiology

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Exercise training (ExT) normalizes the increased sympathetic outflow in chronic heart failure (HF). The underlying mechanisms are not clearly understood. We hypothesized that ExT normalized the blunted central component of the baroreflex control of renal sympathetic nerve activity (RSNA) in HF. Four groups of rats [sham operated (sham)-sedentary (Sed), sham-ExT, HF-Sed, and HF-ExT] were used. HF was induced by left coronary artery ligation, and ExT consisted of 3 wk of treadmill running. In anesthetized rats, the decrease in RSNA in response to aortic depressor nerve stimulation (5-40 Hz) in the HF-Sed group was significantly lower than that in the sham-Sed group (-37 ± 7% vs. -63 ± 8% at 40 Hz, P < 0.05). In the HF-ExT group, responses in RSNA, mean arterial pressure (MAP), and heart rate (HR) were not significantly different from those in the sham-Sed or sham-ExT groups. ExT normalized blunted RSNA, MAP, and HR responses to bicuculline microinjections into the paraventricular nucleus (PVN) in rats with HF. Activation of the PVN by blockade of GABA receptors with bicuculline in normal control rats blunted the centrally component of the baroreflex arc. GABAA-α1 and -β1 receptor protein expression were significantly lower (by 48% and 30%) in the HF-Sed group, but ExT normalized this difference between the HF and sham groups. These data suggest that one mechanism by which ExT alleviates elevated sympathetic outflow in HF may be through normalization of central integrative mechanisms, perhaps via improving the inhibitory GABAergic mechanism within the PVN, on the baroreflex arc.

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“…In fact, increasing MIF levels in the PVN of Sprague-Dawley rats had the seemingly adverse effect of reducing baroreflex sensitivity. The PVN exerts tonic inhibition on baroreflex function (46); however, the mechanism accounting for the effect of excess MIF to inhibit baro- GFP time control, n ϭ 6; MIF time control, n ϭ 7-8; GFP stress, n ϭ 9; MIF stress, n ϭ 13. *P Ͻ 0.05 MIF vs. GFP, #P Ͻ 0.05 stress vs. time control.…”

Section: Discussionmentioning

confidence: 99%

Novel mechanism within the paraventricular nucleus reduces both blood pressure and hypothalamic pituitary-adrenal axis responses to acute stress

Erdös

Clifton

et al. 2015

American Journal of Physiology-Heart and Circulatory Physiology

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Erdos B, Clifton RR, Liu M, Li H, McCowan ML, Sumners C, Scheuer DA. Novel mechanism within the paraventricular nucleus reduces both blood pressure and hypothalamic pituitary-adrenal axis responses to acute stress. Am J Physiol Heart Circ Physiol 309: H634-H645, 2015. First published June 12, 2015 doi:10.1152/ajpheart.00207.2015.-Macrophage migration inhibitory factor (MIF) counteracts pressor effects of angiotensin II (ANG II) in the paraventricular nucleus of the hypothalamus (PVN) in normotensive rats, but this mechanism is absent in spontaneously hypertensive rats (SHRs) due to a lack of MIF in PVN neurons. Since endogenous ANG II in the PVN modulates stress reactivity, we tested the hypothesis that replacement of MIF in PVN neurons would reduce baseline blood pressure and inhibit stressinduced increases in blood pressure and plasma corticosterone in adult male SHRs. Radiotelemetry transmitters were implanted to measure blood pressure, and then an adeno-associated viral vector expressing either enhanced green fluorescent protein (GFP) or MIF was injected bilaterally into the PVN. Cardiovascular responses to a 15-min water stress (1-cm deep, 25°C) and a 60-min restraint stress were evaluated 3-4 wk later. MIF treatment in the PVN attenuated average restraintinduced increases in blood pressure (37.4 Ϯ 2.0 and 27.6 Ϯ 3.5 mmHg in GFP and MIF groups, respectively, P Ͻ 0.05) and corticosterone (42 Ϯ 2 and 36 Ϯ 3 g/dl in GFP and MIF groups, respectively, P Ͻ 0.05). MIF treatment in the PVN also reduced stress-induced elevations in the number of c-Fos-positive cells in the rostral ventrolateral medulla (71 Ϯ 5 in GFP and 47 Ϯ 5 in MIF SHRs, P Ͻ 0.01) and corticotropin-releasing factor mRNA expression in the PVN. However, MIF had no significant effects on the cardiovascular responses to water stress in SHRs or to either stress in Sprague-Dawley rats. Therefore, viral vector-mediated restoration of MIF in PVN neurons of SHRs attenuates blood pressure and hypothalamic pituitary adrenal axis responses to stress. psychological stress; blood pressure; brain; angiotensin ii; hypertension NEW & NOTEWORTHY Exaggerated activation of the sympathetic nervous system and/or the hypothalamic-pituitary-adrenal (HPA) axis increases cardiovascular disease risk. The present study demonstrates that macrophage migration inhibitory factor (MIF) in paraventricular nucleus (PVN) neurons is a novel mechanism mediating attenuation of both the sympathetic and HPA axis responses to acute stress.SEVERAL LINES OF EVIDENCE suggest that the amplitude of blood pressure increases in response to psychological or physical stressors in young and middle-aged normotensive adults elevates the risk of developing hypertension and other cardiovascular diseases such as coronary artery disease, myocardial ischemia, and stroke later in their life (8,20,39,41,42,44,50,60). Larger variations in blood pressure in response to repeated everyday stressors may lead to accelerated damage of the kidneys and vasculature. Altered central mechanisms that mediate augmented...

show abstract

GABA in the paraventricular nucleus tonically suppresses baroreflex function: alterations during pregnancy

Cited by 17 publications

References 34 publications

Hypothalamic Paraventricular and Arcuate Nuclei Contribute to Elevated Sympathetic Nerve Activity in Pregnant Rats

Hypothalamic Paraventricular and Arcuate Nuclei Contribute to Elevated Sympathetic Nerve Activity in Pregnant Rats

Exercise training normalizes the blunted central component of the baroreflex in rats with heart failure: role of the PVN

Novel mechanism within the paraventricular nucleus reduces both blood pressure and hypothalamic pituitary-adrenal axis responses to acute stress

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