TY - JOUR
T1 - Orexin A in rat rostral ventrolateral medulla is pressor, sympatho-excitatory, increases barosensitivity and attenuates the somato-sympathetic reflex
AU - Shahid, Israt Z.
AU - Rahman, Ahmed A.
AU - Pilowsky, Paul M.
PY - 2012/4
Y1 - 2012/4
N2 - BACKGROUND AND PURPOSE 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. EXPERIMENTAL APPROACH 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. KEY RESULTS 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. CONCLUSIONS AND IMPLICATIONS 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.
AB - BACKGROUND AND PURPOSE 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. EXPERIMENTAL APPROACH 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. KEY RESULTS 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. CONCLUSIONS AND IMPLICATIONS 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.
KW - baroreflex
KW - chemoreflex
KW - orexin A
KW - somato-sympathetic reflex
KW - sympathetic vasomotor tone
UR - http://www.scopus.com/inward/record.url?scp=84858187338&partnerID=8YFLogxK
U2 - 10.1111/j.1476-5381.2011.01694.x
DO - 10.1111/j.1476-5381.2011.01694.x
M3 - Article
C2 - 21951179
AN - SCOPUS:84858187338
SN - 0007-1188
VL - 165
SP - 2292
EP - 2303
JO - British Journal of Pharmacology
JF - British Journal of Pharmacology
IS - 7
ER -