Cardiovascular and sympathoadrenal responses to intrathecal injection of neuropeptide K in the conscious rat.

In the conscious freely moving rat, the intrathecal (i.t.) injection of neuropeptide K (NPK; 0.65 to 6.5 nmol), at T-9 spinal cord level, produced dose-dependent and prolonged (> 3 h) increases in mean arterial blood pressure (MAP) and heart rate (HR). The cardiovascular response to 3.25 nmol NPK was less sustained when injected at T-2 level. The cardiovascular response to 3.25 nmol NPK (T-9 level) was correlated with increases in plasma levels of noradrenaline, adrenaline and neuropeptide Y (NPY), and was significantly reduced by the prior i.v. administration of inhibitors of either alpha-adrenoceptors (1 mg/kg, phentolamine), alpha 1-adrenoceptors (1 mg/kg, prazosin), beta 1-adrenoceptors (1 mg/kg, metoprolol) or angiotensin converting enzyme (10 mg/kg, captopril). The cardiovascular response to NPK was also significantly reduced in rats that had undergone, 48 h earlier, bilateral adrenalectomy or to a greater extent sympathectomy with 6-hydroxydopamine. Whereas NPK-induced release of adrenaline was abolished by adrenalectomy, that of neuropeptide Y and noradrenaline was blunted by either treatment. The results suggest that the cardiovascular effect of i.t. NPK is mediated by the stimulation of the sympathoadrenal system and the release of angiotensin. Sympathetic fibers may play a greater role than the adrenal medulla in the cardiovascular response to NPK. It appears that neuropeptide Y derives from both sympathetic fibers and adrenal medullae. Hence, if released in the spinal cord, NPK may play an important role in cardiovascular and sympathoadrenal regulation.