Central action of orexins on sympathetic outflow and cardiovascular function with a focus on the paraventricular nucleus of the hypothalamus

Orexins were initially reported as regulators of food intake. More recent reports suggest that they might play roles in the multiple functions of neuronal systems, causing medical conditions such as narcolepsy, a sleep disorder. Orexins and their receptors (OX1R and OX2R) are distributed in the neural tissue and brain regions involved in the autonomic and neuroendocrine control. Within the hypothalamus, orexin fibers and orexin receptors, especially OX2R, are found extensively in the paraventricular nucleus (PVN) of the hypothalamus. The PVN is an integrative center of the autonomic nervous system and the neuroendocrine system. Thus, orexins may play a role in the regulation of cardiovascular and autonomic nervous systems. This article provides a summary of our studies, in which we used direct recording of renal sympathetic nerve and PVN neuronal activities in conscious freely-moving rats and the in vitro whole cell patch-clamp technique to examine the direct effect of orexins on PVN neurons using a hypothalamic slice. Functional studies demonstrated that intracerebroventricularly (i.c.v.) administered orexins evoke increases in blood pressure, heart rate, and sympathetic nerve activity and depolarize both the magno- and parvo-cellular neurons through the activation of non-selective cation channels. The present studies suggest that PVN plays a role as one of the efferent pathways of orexin-induced activation of the sympathetic outflow.