ORGANIC OSMOLYTES IN RAT RENAL INNER MEDULLA ARE MODULATED BY VASOPRESSIN V-1 AND/OR V-2 ANTAGONISTS

For the purpose of clarifying the role of vasopressin V-1 and V-2 receptors in osmolyte accumulation, we determined the effects on the inner medullary osmolyte content of the administration of orally active vasopressin V-1 and/or V-2 receptor antagonists OPC-21268 (i.e., 1-{1-[4-(3-acetylaminopropoxy)benzoyl]-4-piperidyl}-3,4-dihydro-2(1H)-quinolinone) and OPC-31260 {i.e., 5-dimethylamino-1-[4 (2-methylbenzoylamino)benzoyl] 2,3,4,5-tetrahydro- 1H-benzazepine} under a condition of maximal urine concentration achieved by water deprivation for 4 days. Taurine content increased significantly with the use of the V-2 antagonist, irrespective of the use of the V-1 antagonist. Inner medullary betaine content decreased with the administration of the V-1 antagonist, irrespective of the administration of V-2 antagonist. The administration of either the V-1 or V-2 antagonist alone did not affect sorbitol content, aldose reductase activity, or aldose reductase mRNA abundance in renal inner medulla. However, the combined administration of the V-1 and V-2 antagonists decreased all of these significantly. Myo-inositol content was not affected by the administration of the V-1 or V-2 antagonists. Glycerophosphorylcholine content was decreased with the use of the V-2 antagonist, irrespective of the use of the V-1 antagonist, and this effect paralleled urine osmolality. In conclusion, the individual organic osmolytes responded differently to the antagonists of vasopressin V-1 and/or V-2 receptors. The mechanisms linked to vasopressin V-1 and/or V-2 receptors appeared to modulate the accumulation of some organic osmolytes in the inner medulla. Aldose reductase mRNA abundance and sorbitol accumulation in the inner medulla appeared to be mediated through either V-1 or V-2 receptors. Taurine accumulation might be inhibited by the V-2 receptor-linked mechanism, and betaine accumulation might be accelerated by the V-1 receptor-linked mechanism.