Respiratory and cardiovascular actions of orexin-A in mice.

Ample evidence has been reported to show a probable contribution of orexin in the central cardiovascular regulation. Although cardiovascular and respiratory centers in the brain are located close to each other and are interconnected, the possible participation of orexin in respiratory regulation has not been fully documented. Here we examined the effects of intracerebroventricular administration of orexin-A on respiratory and cardiovascular parameters in urethane-anesthetized mice. Respiratory frequency and tidal volume were recorded simultaneously with blood pressure and heart rate. Orexin-A (0.003-3 nmol in 2 microL) or vehicle was administered into the lateral ventricle or cisterna magna. Lateral ventricular administration induced a rise in respiratory frequency (by 11% at the highest dose), tidal volume (76%), blood pressure (13%) and heart rate (6%) in a dose-dependent manner. With intracisternal administration, however, respiratory frequency did not change while a similar increase in tidal volume (75%) was observed. A relatively larger cardiovascular response was elicited with intracisternal administration (blood pressure 26%, heart rate 9%). On the other hand, with either administration route, orexin-A did not affect reflex increases in respiratory frequency and tidal volume in response to hypoxia and hypercapnia. These results show possible participation of orexin-A not only in the cardiovascular regulation but also in the respiratory control system. Moreover, orexin can affect the cardiorespiratory control system at multiple sites in different ways. Orexin-A seems not to be involved in respiratory reflex regulation in mice at least under anesthetized condition.