Prehypertensive juvenile spontaneously hypertensive rats have more orexin neurons than normotensive Wistar Kyoto rats

The neuropeptide orexin contributes to the regulation of blood pressure as part of its role in the control of arousal during wakefulness and motivated behavior. Recent work has suggested that an upregulated orexinergic system may contribute to the hypertensive phenotype of the SHR, with adult SHRs having significantly higher numbers of orexin neurons in the medial, but not lateral hypothalamus as compared to normotensive WKY and Wistar rats. (Clifford et al. 2015, Exp Physiol). However it is not known whether this upregulation is causing, or secondary to hypertensive pathologies seen in SHR periphery organs. As SHRs develop hypertension at 6 weeks of age, we sought to investigate the orexin system of prehypertensive SHRs. Aim: To determine the number of orexin neurons in young SHR and WKY rats before hypertension develops. Methods: Juvenile (3-5 weeks old) SHR (n = 8) and Wistar Kyoto (WKY, n = 8) male rats were euthanized, perfused and their brains sectioned and immunolabelled for orexin A. Labelled neurons were plotted and counted in the six densest hemisections (120 μm apart) of each brain. Results: There was a significantly higher number of orexin neurons (~ + 45%) in both the medial hypothalamus (medial to fornix) in hypertensive SHRs when compared to normotensive WKYs (119 ± 4 vs 86 ± 5, p < 0.0001 per hemisection) and the lateral hypothalamus (72 ± 3 vs 47 ± 3 per hemisection, p < 0.0001). Conclusion: These results show that the orexinergic system is highly upregulated in young SHRs well before hypertension develops, suggesting that hypertensive periphery develops in response to this increased sympathetic output.