Excessive Respiratory Modulation of Blood Pressure Triggers Hypertension

Menuet, Clément; Shen, Le; Dempsey, Bowen; Connelly, Angela A.; Kamar, Jessica; Jancovski, Nikola; Bassi, Jaspreet K; Walters, Keryn; Simms, Annabel E.; Hammond, Andrew; Fong, Angelina Y.; Goodchild, Ann K.; McMullan, Simon; Allen, Andrew M.

doi:10.1016/j.cmet.2017.01.019

Cited by 61 publications

(97 citation statements)

References 45 publications

(52 reference statements)

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“…Allatostatin is soluble in saline and water and is fast acting (Haettig et al, 2013). Electrophysiological recordings of allatostatin receptor-transduced neurons show neuronal silencing within minutes of bath application of allatostatin (Tan et al, 2006), which is recovered within minutes following washout (Menuet et al, 2017;Tan et al, 2006). Haettig et al (2013) used this technique to inactivate CA1 hippocampal interneurons and showed impairments in long-term memory for object location.…”

Section: Ligand-gated G Proteins: Allatostatin Neuropeptide Receptormentioning

confidence: 99%

“…Haettig et al (2013) used this technique to inactivate CA1 hippocampal interneurons and showed impairments in long-term memory for object location. Additionally, Menuet et al (2017) used the allatostatin receptor to show a functional link between respiratory modulation of BP and hypertension via the inhibition of rostral ventrolateral medulla adrenergic (C1) neurons. Importantly though, allatostatin does not cross the blood-brain barrier (BBB), limiting its clinical potential.…”

Section: Ligand-gated G Proteins: Allatostatin Neuropeptide Receptormentioning

confidence: 99%

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The use of chemogenetics in behavioural neuroscience: receptor variants, targeting approaches and caveats

Campbell

Marchant

2018

British J Pharmacology

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The last decade has seen major advances in neuroscience tools allowing us to selectively modulate cellular pathways in freely moving animals. Chemogenetic approaches such as designer receptors exclusively activated by designer drugs (DREADDs) permit the remote control of neuronal function by systemic drug administration. These approaches have dramatically advanced our understanding of the neural control of behaviour. Here, we review the different techniques and genetic approaches available for the restriction of chemogenetic receptors to defined neuronal populations. We highlight the use of a dual virus approach to target specific circuitries and the effectiveness of different routes of administration of designer drugs. Finally, we discuss the potential caveats associated with DREADDs including off-target effects of designer drugs, the effects of chronic chemogenetic receptor activation and the issue of collateral projections associated with DREADD activation and inhibition. AbbreviationsAAVs, adeno-associated viral vectors; BBB, blood-brain barrier; CAMKII, calmodulin-dependent protein kinase II; CAVs, canine adenoviruses; CNO, clozapine N-oxide; DREADDs, designer receptors exclusively activated by designer drugs; hM3D, human M 3 muscarinic DREADD; hM4D, human M 4 muscarinic DREADD; HSV, herpes simplex viral; hSyn, human synapsin; KORD, κ-opioid-based receptor designer receptor exclusively activated by designer drugs; LGICs, ligand-gated ion channels; NAc, nucleus accumbens; RASSL, receptor activated solely by a synthetic ligand; SalB, salvinorin B; VTA, ventral tegmental area IntroductionDuring the last decade, there has been a revolution in neuroscience techniques that have resulted in increasingly precise methods to manipulate neural systems in awake, behaving animals. Understanding the relationship between brain function and behaviour is critical for the advancement of both neuroscience research and targeted medication development. Chemogenetics refers to the technique that allows for the reversible remote control of cell populations and neural circuitry via systemic injection or microinfusion of an activating ligand (Alexander et al., 2009;Armbruster et al., 2007). The chemogenetic technique uses engineered receptors and biologically inert ligands to achieve this aim. Unlike optogenetics, which has the ability to control cells and neural circuitry with light, the use of designer drugs makes chemogenetics simple to use, removing the need for optical fibre probes and tethers. While the temporal resolution of chemogenetics is lower than optogenetics, this relatively non-invasive technique is still effective for functional mapping, cell-type-specific manipulations and multiplexed control of neurons.In this review, we will evaluate the different strategies that have been used to restrict chemogenetic receptors to defined neuronal populations. We will also highlight the use of a dual virus approach at targeting projection neurons and the effectiveness of different routes of administration of designer drugs. Fin...

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Section: Ligand-gated G Proteins: Allatostatin Neuropeptide Receptormentioning

confidence: 99%

Section: Ligand-gated G Proteins: Allatostatin Neuropeptide Receptormentioning

confidence: 99%

The use of chemogenetics in behavioural neuroscience: receptor variants, targeting approaches and caveats

Campbell

Marchant

2018

British J Pharmacology

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“…This hyperactivity was present in the PHSH rat before both the onset of hypertension and the deficit in sympathetic innervation; whether it persists in adulthood is unknown but based on other sympathetic outflows recorded previously from SHR (Menuet et al . ), we would predict it would. One possibility is that this excessive sympathetic activity leads to the demise of the DBH immunopositive innervation as has been found to occur to noradrenergic nerves innervating cardiac tissue in heart failure (Igawa et al .…”

Section: Discussionmentioning

confidence: 85%

Differences in autonomic innervation to the vertebrobasilar arteries in spontaneously hypertensive and Wistar rats

Roloff

Walas

Moraes

et al. 2018

The Journal of Physiology

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Neurogenic hypertension may result from brainstem hypoperfusion. We previously found remodelling (decreased lumen, increased wall thickness) in vertebrobasilar arteries of juvenile, pre-hypertensive spontaneously hypertensive (PHSH) and adult spontaneously hypertensive (SH) rats compared to age-matched normotensive rats. We tested the hypothesis that there would be a greater density of sympathetic to parasympathetic innervation of vertebrobasilar arteries in SH versus Wistar rats irrespective of the stage of development and that sympathetic denervation (ablation of the superior cervical ganglia bilaterally) would reverse the remodelling and lower blood pressure. Contrary to our hypothesis, immunohistochemistry revealed a decrease in the innervation density of noradrenergic sympathetic fibres in adult SH rats (P < 0.01) compared to Wistar rats. Unexpectedly, there was a 65% deficit in parasympathetic fibres, as assessed by both vesicular acetylcholine transporter (α-VAChT) and vasoactive intestinal peptide (α-VIP) immunofluorescence (P < 0.002) in PHSH rats compared to age-matched Wistar rats. Although the neural activity of the internal cervical sympathetic branch, which innervates the vertebrobasilar arteries, was higher in PHSH relative to Wistar rats, its denervation had no effect on the vertebrobasilar artery morphology or persistent effect on arterial pressure in SH rats. Our neuroanatomic and functional data do not support a role for sympathetic nerves in remodelling of the vertebrobasilar artery wall in PHSH or SH rats. The remodelling of vertebrobasilar arteries and the elevated activity in the internal cervical sympathetic nerve coupled with their reduced parasympathetic innervation suggests a compromised vasodilatory capacity in PHSH and SH rats that could explain their brainstem hypoperfusion.

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“…The role of the high‐frequency component of BPV in autonomic regulation is less clear, however, a recent report indicated that it may be linked to respiratory modulation of sympathetic vasomotor tone (Menuet et al. ). Although we failed to identify any clear differences in BPV between groups, it is possible that differences may arise in later childhood.…”

Section: Discussionmentioning

confidence: 99%

Noninvasive assessment of autonomic function in human neonates born at the extremes of fetal growth spectrum

et al. 2018

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Birth weight is associated with adult cardiovascular disease, such that those at both ends of the spectrum are at increased risk. This may be driven in part by modification to autonomic control, a mechanistic contributor to hypertension. However, birth weight is a relatively crude surrogate of fetal growth; and newborn body composition may more accurately identify the “at risk” infant. Accordingly, we sought to determine whether newborns with high or low body fat have altered autonomic control of vasomotor function and cardiac contractility. Body fat was assessed by air‐displacement plethysmography <24 h postnatal. Measures of spontaneous baroreflex sensitivity (sBRS), blood pressure variability (BPV), and dP/dt max variability were compared between newborns categorized according to established body fat percentiles: high body fat (HBF, >90th percentile, n = 7), low body fat (LBF, ≤10th percentile, n = 12), and normal body fat (control, >25th to ≤75th percentile, n = 23). BPV was similar across body fat percentiles; similarly, low frequency dP/dt max variability was similar across body fat percentiles. sBRS was reduced in HBF compared to controls (11.0 ± 6.0 vs. 20.1 ± 9.4 msec/mmHg, P = 0.03), but LBF did not differ (18.4 ± 6.0 msec/mmHg, P = 0.80). Across the entire body fat spectrum (n = 62), there was a nonlinear association between newborn body fat and sBRS (P = 0.03) that was independent of birth weight (P = 0.04). Autonomic modulation of vasomotor function and cardiac contractility in the newborn did not differ by body fat, but newborns born with high body fat show depressed baroreflex sensitivity.

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Excessive Respiratory Modulation of Blood Pressure Triggers Hypertension

Cited by 61 publications

References 45 publications

The use of chemogenetics in behavioural neuroscience: receptor variants, targeting approaches and caveats

The use of chemogenetics in behavioural neuroscience: receptor variants, targeting approaches and caveats

Differences in autonomic innervation to the vertebrobasilar arteries in spontaneously hypertensive and Wistar rats

Noninvasive assessment of autonomic function in human neonates born at the extremes of fetal growth spectrum

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