Article

Orexin A in rat rostral ventrolateral medulla is pressor, sympatho-excitatory, increases barosensitivity and attenuates the somato-sympathetic reflex.

Australian School of Advanced Medicine, Macquarie University, Sydney, Australia.
British Journal of Pharmacology (impact factor: 4.41). 09/2011; 165(7):2292-303. DOI:10.1111/j.1476-5381.2011.01694.x pp.2292-303
Source: PubMed

ABSTRACT The rostral ventrolateral medulla (RVLM) maintains sympathetic nerve activity (SNA), and integrates adaptive reflexes. Orexin A-immunoreactive neurones in the lateral hypothalamus project to the RVLM. Microinjection of orexin A into RVLM increases blood pressure and heart rate. However, the expression of orexin receptors, and effects of orexin A in the RVLM on splanchnic SNA (sSNA), respiration and adaptive reflexes are unknown.
The effect of orexin A on baseline cardio-respiratory variables as well as the somato-sympathetic, baroreceptor and chemoreceptor reflexes in RVLM were investigated in urethane-anaesthetized, vagotomized and artificially ventilated male Sprague-Dawley rats (n= 50). orexin A and its receptors were detected with fluorescence immunohistochemistry.
Tyrosine hydroxylase-immunoreactive neurones in the RVLM were frequently co-localized with orexin 1 (OX(1) ) and orexin 2 (OX(2) ) receptors and closely apposed to orexin A-immunoreactive terminals. Orexin A injected into the RVLM was pressor and sympatho-excitatory. Peak effects were observed at 50 pmol with increased mean arterial pressure (42 mmHg) and SNA (45%). Responses to orexin A (50 pmol) were attenuated by the OX(1) receptor antagonist, SB334867, and reproduced by the OX(2) receptor agonist, [Ala(11) , D-Leu(15) ]orexin B. Orexin A attenuated the somato-sympathetic reflex but increased baroreflex sensitivity. Orexin A increased or reduced sympatho-excitation following hypoxia or hypercapnia respectively.
Although central cardio-respiratory control mechanisms at rest do not rely on orexin, responses to adaptive stimuli are dramatically affected by the functional state of orexin receptors.

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  • Article: Guide to Receptors and Channels (GRAC), 5th edition.
    Stephen P H Alexander, Alistair Mathie, John A Peters
    [show abstract] [hide abstract]
    ABSTRACT: The Fifth Edition of the 'Guide to Receptors and Channels' is a compilation of the major pharmacological targets divided into seven sections: G protein-coupled receptors, ligand-gated ion channels, ion channels, catalytic receptors, nuclear receptors, transporters and enzymes. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside suggestions for further reading. Available alongside this publication is a portal at http://www.GuideToPharmacology.org which is produced in close association with NC-IUPHAR and allows free online access to the information presented in the Fifth Edition.
    British Journal of Pharmacology 11/2011; 164 Suppl 1:S1-324. · 4.41 Impact Factor
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.

Keywords

adaptive reflexes
 
adaptive stimuli
 
arterial pressure
 
baroreflex sensitivity
 
baseline cardio-respiratory variables
 
central cardio-respiratory control mechanisms
 
heart rate
 
integrates adaptive reflexes
 
orexin 1
 
orexin 2
 
Orexin A-immunoreactive neurones
 
orexin A-immunoreactive terminals
 
orexin receptors
 
Peak effects
 
rostral ventrolateral medulla
 
RVLM increases blood pressure
 
somato-sympathetic reflex
 
splanchnic SNA
 
sympathetic nerve activity
 
Tyrosine hydroxylase-immunoreactive neurones