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The Enhanced CO 2 Chemoreflex is Associated with Increased Number of CO 2 ‐activated Orexin Neurons in the Lateral Hypothalamus in Spontaneously Hypertensive Rats (SHRs)
Author(s) -
Li Aihua,
Nattie Eugene,
Roy Sarah
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.772.7
Subject(s) - orexin , endocrinology , medicine , chemistry , orexin a , orexin receptor , lateral hypothalamus , antagonist , chemoreceptor , baroreflex , hypothalamus , receptor , blood pressure , neuropeptide , heart rate
Activation of central chemoreceptors by CO 2 increases arterial blood pressure (ABP), sympathetic nerve activity (SNA), and breathing. Experiments using SHRs, a well‐established neurogenic hypertensive model, have shown that the high ABP is associated with elevated SNA and peripheral chemoreflexes, and an impaired baroreflex. We have showed that: 1) SHRs have an age‐dependent increase in CO 2 chemoreflex and ABP; 2) the increased CO 2 chemoreflex and ABP are measureable in juveniles (P28–50); 3) the enhanced CO 2 chemoreflex persists while peripheral chemoreceptors were inhibited by hyperoxia indicating an important role for central chemoreflex in neurogenic hypertension; and 4) blocking orexin receptors with a dual orexin receptor antagonist, Almorexant (Almxt), can normalize the enhanced CO 2 chemoreflex and significantly lower high ABP in SHRs. In this study, we evaluated CO 2 ‐activated c‐fos expression in orexin neurons in both hypertensive (SHRs) and normotensive control (WKY) rats, and hypothesized that the enhanced CO 2 chemoreflex observed in SHRs is associated with increased number of CO 2 ‐activated c‐fos expressing orexin neurons in the lateral hypothalamic area (LHA). The rats were exposed to 7%CO 2 for 1.5hr, and sections of LHA were double stained for c‐fos and orexin‐A. The Stereo Investigator System was used for the cell counts. The results show that in the LHA, SHRs have: 1) more orexin‐containing neurons (~28%), similar as some recent reports, and 2) more CO 2 ‐induced c‐fos and orexin double‐expressing neurons (~71%) than that of age‐matched normotensive WKY rats. We conclude that the enhanced CO 2 chemoreflex in SHRs is associated with the overactive orexin system, and modulation of this overactive orexin system and CO 2 chemoreflex could be beneficial in treating neurogenic hypertension. Support or Funding Information NIH HL 28066