In vivo gene transfer methods for studying the modulation of cardiorespiratory reflexes by the nucleus of the solitary tract (NTS)

Won, L.F.; Edwards, Emma; Kasparov, Sergey; Murphy, D.; Paton, JF

doi:10.1016/s1566-0702(00)00266-6

Autonomic Neuroscience

2001

DOI: 10.1016/s1566-0702(00)00266-6

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In vivo gene transfer methods for studying the modulation of cardiorespiratory reflexes by the nucleus of the solitary tract (NTS)

L.F. Won¹,

Emma Edwards²,

Sergey Kasparov³

et al.

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“…A combination of pharmacological and genetic tools was used in an unanesthetized decerebrate rat model to determine whether PLCmediated Ca 2ϩ release or ROS/PI3K/Akt pathways are essential for inhibition of the baroreflex by ANG II. Preliminary reports of parts of this study have been presented (20).…”

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Genetic and pharmacological dissection of pathways involved in the angiotensin II‐mediated depression of baroreflex function

et al. 2002

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Heart failure and hypertension are associated with increases in angiotensin II (ANG II) activity. One brain area where ANG II effects may be particularly important in these situations is the nucleus of the solitary tract (NTS). Located in the dorsomedial medulla, the NTS is the termination site of baroreceptor afferents and is essential for mediating the baroreflex. In hypertensive animals the baroreflex is impaired; this may be reversed by antagonizing ANG II AT1 receptors in the NTS. Recently, we showed that the baroreflex depressant action of ANG II in the NTS is mediated by activation of endothelial nitric oxide synthase (eNOS) and enhanced release of GABA. Using conventional pharmacological tools and a range of adenoviral-mediated expression of dominant negative proteins, we have determined the intracellular pathway(s) in the NTS by which ANG II activates eNOS. Our data indicate that ANG II acting in the NTS depresses the baroreflex via a Gq protein-mediated activation of phospholipase C, which through 1,4,5-inositol triphosphate causes release of calcium from the IP3-sensitive intracellular stores and calcium-calmodulin formation. In contrast, multiple site disruption of a pathway leading to eNOS activation via the serine/threonine kinase Akt was ineffective

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confidence: 99%

Genetic and pharmacological dissection of pathways involved in the angiotensin II‐mediated depression of baroreflex function

et al. 2002

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In vivo gene transfer methods for studying the modulation of cardiorespiratory reflexes by the nucleus of the solitary tract (NTS)

Cited by 1 publication

References 0 publications

Genetic and pharmacological dissection of pathways involved in the angiotensin II‐mediated depression of baroreflex function

Genetic and pharmacological dissection of pathways involved in the angiotensin II‐mediated depression of baroreflex function

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