Organic osmolytes in rat renal inner medulla are modulated by vasopressin V1 and/or V2 antagonists.
For the purpose of clarifying the role of vasopressin V1 and V2 receptors in osmolyte accumulation, we determined the effects on the inner medullary osmolyte content of the administration of orally active vasopressin V1 and/or V2 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-tet rah ydro-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 V2 antagonist, irrespective of the use of the V1 antagonist. Inner medullary betaine content decreased with the administration of the V1 antagonist, irrespective of the administration of V2 antagonist. The administration of either the V1 or V2 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 V1 and V2 antagonists decreased all of these significantly. Myo-inositol content was not affected by the administration of the V1 or V2 antagonists. Glycerophosphorylcholine content was decreased with the use of the V2 antagonist, irrespective of the use of the V1 antagonist, and this effect paralleled urine osmolality. In conclusion, the individual organic osmolytes responded differently to the antagonists of vasopressin V1 and/or V2 receptors. The mechanisms linked to vasopressin V1 and/or V2 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 V1 or V2 receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
Nakanishi
T
T
Fifth Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.
Yamauchi
A
A
Nakahama
H
H
Yamamura
Y
Y
Yamada
Y
Y
Orita
Y
Y
Fujiwara
Y
Y
Uyeda
N
N
Takamitsu
Y
Y
Sugita
M
M
D000449:Aldehyde Reductase / Q000378:metabolism; D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists; D001552:Benzazepines / Q000494:pharmacology*; D004231:Diuresis; D007679:Kidney Medulla / Q000378:metabolism*; D008297:Male; D009994:Osmolar Concentration; D009995:Osmosis; D010880:Piperidines / Q000494:pharmacology*; D015363:Quinolones / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014556:Urine / Q000737:chemistry; D014868:Water Deprivation / Q000502:physiology
D065092:Antidiuretic Hormone Receptor Antagonists; D001552:Benzazepines; D010880:Piperidines; D015363:Quinolones; D012333:RNA, Messenger; C068644:OPC 21268; C076251:mozavaptan; D000449:Aldehyde Reductase