Potent depressor action of leumorphin, a kappa-opioid agonist, in conscious rats

To investigate the role of leumorphin, a kappa-opioid agonist derived from proenkephalin B (neoendorphin/dynorphin precursor) in the central cardiovascular control, the effects of intracerebroventricular (ICV) administration of leumorphin on basal blood pressure and angiotensin II (AII)-stimulated pressor response were examined in conscious unrestrained rats. The ICV injection of 0.06 and 0.6 nmol of leumorphin caused a significant decrease in basal blood pressure (delta mean arterial pressure (MAP): -6.5 +/- 2.7 and -7.2 +/- 1.7 mm Hg, respectively). The ICV injection of AII (0.1 nmol) elicited a pressor response (delta MAP: 21.4 +/- 1.1 mm Hg). This pressor response was significantly reduced by the simultaneous administration of leumorphin, and furthermore, the blood pressure was lowered below the basal level. These depressor actions of leumorphin were partially antagonized by the preadministration of naloxone, an opiate antagonist. These results together with our previous works on the potent inhibitory actions of leumorphin on drinking and vasopressin secretion suggest the possible involvement of leumorphin in the central regulation of blood pressure and body fluid homeostasis.