A common neuronal mechanism of hypertension and sleep disturbances in spontaneously hypertensive rats: Role of orexinergic neurons.

Epidemiologic studies have shown that sleep disorders are associated with the development of hypertension. The present study investigated dynamic changes in sleep patterns during the development of hypertension across the lifespan in spontaneously hypertensive rats (SHRs) and the neural mechanism that underlies these comorbidities, with a focus on the orexinergic system. Blood pressure in rats was measured using a noninvasive blood pressure tail cuff. Sleep was monitored by electroencephalographic and electromyographic recordings. Immunohistochemistry was used to detect the density and activity of orexinergic neurons in the perifornical nucleus. Hcrt2-SAP (400 or 800 ng) was microinjected in the lateral hypothalamus to lesion orexinergic neurons. Compared with Wistar-Kyoto rats, SHRs exhibited various patterns of sleep disturbances. In SHRs, dynamic changes in hypersomnia in the rats' active phase was not synchronized with the development of hypertension, but hyperarousal in the inactive phase and difficulties in falling asleep were observed concurrently with the development of hypertension. Furthermore, the density and activity of orexinergic neurons in the perifornical nucleus were significantly higher in SHRs than in age-matched Wistar-Kyoto rats. The reduction of orexinergic neurons in the lateral hypothalamus partially ameliorated the development of hypertension and prevented difficulties in falling asleep in SHRs. These results indicate that although the correlation between sleep disturbances and hypertension is very complex, common mechanisms may underlie these comorbidities in SHRs. Overactivity of the orexin system may be one such common mechanism.