Inhibition of elevated arginine vasopressin secretion in response to osmotic stimulation and acute haemorrhage by U-62066E, a kappa-opioid receptor agonist

Abstract

1. The effect of kappa (kappa) opioid receptor activation on the increase in arginine vasopressin (AVP) secretion evoked by two acute and quite different stimuli (i.e., haemorrhage and osmotic stimulus due to hypertonic saline infusion) were evaluated in conscious Long-Evans rats, by use of U-62066E, a highly selective kappa-opioid receptor agonist, and MR2266, an opioid receptor antagonist with some selectivity for kappa-receptors. 2. An acute haemorrhage, which reduced the mean blood pressure by approximately 50%, resulted in a large increase in the plasma AVP (pAVP) levels of control rats. However, the administration of U-62066E (0.2 mg kg-1 or 2.0 mg kg-1) reduced the increase due to haemorrhage in a dose-dependent manner. In contrast, concomitant administration of 2.0 mg kg-1 of MR2266 with U-62066E significantly attenuated the inhibition of pAVP levels produced by U-62066E 2.0 mg kg-1. 3. Hypertonic saline infusion (5% hypertonic saline solution at a rate of 0.24 ml kg-1 min-1 for 10 min) caused the elevation of plasma osmolality (pOsm) from 294.0 +/- 1.6 mosmol kg-1 to 304.4 +/- 1.9 mosmol kg-1, simultaneously resulting in a significant increase in pAVP levels from 2.34 +/- 0.28 pg ml-1 to 4.54 +/- 0.51 pg ml-1. However, the administration of U-62066E (0.05 mg kg-1 or 0.2 mg kg-1) reduced the osmotically induced increase in pAVP in a dose-dependent manner although pOsm showed the same degree of increase as in controls. In contrast, concomitant administration of 0.2mgkg-1 of MR2266 with U-62066E significantly attenuated the inhibition of pAVP levels produced by U-62066E 0.2mgkg- , whereas pOsm showed the same degree of increase as in controls. No significant changes in the mean blood pressure of the respective groups were observed during this experiment. 4. It is suggested that the Kappa-Opioid receptor activation reduces the increase in AVP secretion evoked by these two different stimuli and that the inhibitory involvement occurs in the neural lobe in the process of AVP secretion.