Chronic central infusion of orexin-A increases arterial pressure in rats.

We determined the cardiovascular responses as well as food and water intakes to chronic intracerebroventricular administration of orexin-A and orexin-B for 14 days in conscious rats. Chronic intracerebroventricular infusion of orexin-A (50 pmol/h) elicited a significant increase in systolic blood pressure on the third day (+15.6 +/- 2.9 mm Hg), and during the continuous intracerebroventricular infusion of orexin-A the blood pressure returned to the baseline levels at day 14. In contrast, chronic intracerebroventricular infusion of orexin-B (50 pmol/h) failed to change systolic blood pressure during the 14 days of experimental periods. Chronic intracerebroventricular infusions of neither orexin-A nor orexin-B changed urinary catecholamine excretions, food and water intakes, and urine volumes at 7 and 14 days of infusion periods. Mean arterial pressure directly measured at 14 days did not differ among the groups of orexin-A, orexin-B, and artificial cerebrospinal fluid treatments. Both intravenous injections of pentolinium (5 mg/kg), a ganglion blocking agent, and CV-11974 (0.05 mg/kg), an AT(1) receptor antagonist, decreased arterial pressure; however, these responses were not different among the groups. These results suggest that central orexin-A participates in the short-term regulation of blood pressure; however, the contributions of central orexins to the long-term regulations of blood pressure, sympathetic nervous system, and appetite may be little.