title: Spontaneously hypertensive rats have more orexin neurons in their medial hypothalamus than normotensive rats.
abstract: What is the central question of this study? Blockade of orexin receptors reduces blood pressure in spontaneously hypertensive rats (SHRs) but not in normotensive Wistar-Kyoto (WKY) rats, suggesting that upregulation of orexin signalling underlies the hypertensive phenotype of the SHR. However, it is not known what causes this upregulation. What is the main finding and its importance? Using orexin immunolabelling, we show that SHRs have 20% more orexin neurons than normotensive WKY and Wistar rats in the medial hypothalamus, which is a good match to their blood pressure phenotype. In contrast, there is no such match for the orexin neurons of the lateral hypothalamus. Essential hypertension may be linked to an increase in orexin neurons in the medial hypothalamus. The neuropeptide orexin contributes to the regulation of blood pressure as part of its role in the control of arousal during wakefulness and motivated behaviour (including responses to psychological stress). Recent work shows that pharmacological blockade of orexin receptors reduces blood pressure in spontaneously hypertensive rats (SHRs) but not in normotensive Wistar-Kyoto (WKY) rats. It is not clear why orexin signalling is upregulated in the SHR, but one possibility is that these animals have more orexin neurons than their normotensive WKY and Wistar relatives. To test this possibility, SHRs, WKY and Wistar male rats (6-16 weeks old) were killed, perfused and their brains sectioned and immunolabelled for orexin A. Labelled neurons were plotted and counted in the six best labelled hemisections (120 μm apart) of each brain. There were significantly more orexin neurons (+20%) in the medial hypothalamus (medial to fornix) of SHRs compared with WKY and Wistar rats (126 ± 4 versus 106 ± 5 and 104 ± 5 per hemisection, respectively, P < 0.05), which matches well the blood pressure phenotypes. In contrast, counts in the lateral hypothalamus did not match the blood pressure phenotypes (69 ± 2 versus 50 ± 3 and 76 ± 4, respectively). The results support the idea that orexin signalling is upregulated in the SHR and suggest that this is due, at least in part, to a greater number of orexin neurons in the medial hypothalamus. These medial orexin neurons, which are also involved in hyperarousal and stress responses, may contribute to the development of essential hypertension.
authors: School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia.
authors: Liam
authors: L
authors: Clifford
authors: Bruno W
authors: BW
authors: Dampney
authors: Pascal
authors: P
authors: Carrive
mesh_terms: D000818:Animals; D001794:Blood Pressure; D006973:Hypertension / Q000503:physiopathology*; D007031:Hypothalamus / Q000473:pathology* / Q000503:physiopathology*; D008297:Male; D009474:Neurons / Q000378:metabolism* / Q000473:pathology*; D000068797:Orexins / Q000378:metabolism*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
chemical_list: D000068797:Orexins