Premium
Orexin A in rat rostral ventrolateral medulla is pressor, sympatho‐excitatory, increases barosensitivity and attenuates the somato‐sympathetic reflex
Author(s) -
Shahid Israt Z,
Rahman Ahmed A,
Pilowsky Paul M
Publication year - 2012
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.2011.01694.x
Subject(s) - rostral ventrolateral medulla , orexin , orexin a , medulla oblongata , medicine , endocrinology , reflex , baroreceptor , orexin receptor , baroreflex , chemistry , receptor , neuropeptide , heart rate , blood pressure , central nervous system
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.