Central Orexin-A Augments Sympathoadrenal Outflow in Conscious Rabbits
Factors regulating food intake, such as leptin and neuropeptide Y, have been shown to participate in central cardiovascular and sympathetic regulations. Orexin-A is a newly discovered hypothalamic peptide that stimulates food intake. The aim of the present study was to determine the neurohormonal and cardiovascular responses to intracerebroventricular administration of orexin-A in conscious rabbits with chronically instrumented electrodes on the renal sympathetic nerve. The experiments were carried out at least 3 days after the surgical procedures. Intracerebroventricular injection of orexin-A elicited dose-related increases in mean arterial pressure and renal sympathetic nerve activity (RSNA). Peak values of mean arterial pressure and RSNA induced by intracerebroventricular injection of 100 pmol of orexin-A (+14.0±0.7 mmHg and +55.4±14.9 %) were obtained at 40 and 25 minutes after injection, respectively. Plasma epinephrine and glucose concentrations significantly increased at 60 and 90 min after intracerebroventricular injection of orexin-A (control vs. 90 min; epinephrine: 38.0±12.8 vs. 167.5±42.5 pg/ml, p<0.01; glucose: 6.66±0.18 vs. 7.75±0.14 mmol/l, p<0.01). Plasma norepinephrine and insulin concentrations increased at 60 and 90 min, but did not reach the significant values. Intracerebroventricular injection of orexin-A also caused significant increases in plasma vasopressin concentrations. However, pretreatment with intravenous injection of pentolinium (5 mg/kg), a ganglion blocking agent, abolished these cardiovascular and neurohormonal responses. On the other hand, intravenous injection of the same dose of orexin-A (100 pmol) as that used in the intracerebroventricular experiment failed to cause any cardiovascular and renal sympathetic nerve responses. These results suggest that intracerebroventricular orexin-A acts in the central nervous system and activates sympathoadrenal outflow, resulting in increases in arterial pressure and plasma glucose levels in conscious rabbits.