ラット凍結脳損傷におけるArginine Vasopressin受容体拮抗剤の抗脳浮腫効果

The Effect of Arginine Vasopressin Receptor Antagonist on the Rat Cold-Injured Brain

I．はじめに

　アルギニンバゾプレッシン（arginine vasopressin以下AVP）は視床下部—下垂体後葉系から血液中へ分泌され，平滑筋収縮作用，抗利尿作用によって循環調節に関与している．さらに，視床下部の室傍核，視索上核などから直接脳内へも分泌され，神経伝達物質として，中枢性循環調節，記憶，摂食行動などに関与していると言われている，一方，近年脳内に分泌されたAVP（中枢性AVP）は正常脳および病的脳において脳血管の水分透過性を亢進させ，脳浮腫が進展する一因であることが報告されている^3,14）．本実験では脳挫傷の実験モデルとされる凍結脳損傷において，脳室内に投与されたAVP受容体拮抗剤が脳水分量，脳組織Na^＋，K^＋含量にどのような影響を与えるか討した．

Centrally released arginine vasopressin (AVP) has been reported to increase the water permeability of brain capillaries under both normal and pathological condi-tions.

It is not known, however, whether AVP regulates the permeability of brain capillaries via a V₁ receptor or a V₂ receptor. In the present experiments, we attempted to suppress cold-induced brain edema with V₁ or V₂ re-ceptor antagonists.

Adult rats were intraventricularly administered with 5 ng, 50 ng, or 500 ng of V₁ receptor antagonist, or 50 ng or 500 ng of V₂ receptor antagonist. Ten minutes after administration, a cold injury was induced in the left hemisphere of the brain by applying a freezing probe, which had been cooled by liquid nitrogen, to the left parietal skull for 20 seconds. Brain water and tissue sodium content were then measured 24 hours after the cold-injury.

In experiment 1, the brain water content had signifi-cantly increased in both the injured and non-injured hemispheres. The administration of 50 ng of V₁ receptor antagonist resulted in a significant reduction in the brain water content of the bilateral hemispheres. Administra-tion of 50 ng of V₂ receptor antagonist produced a signi-ficant reduction in the brain water content of the non-injured hemisphere only. A 500 ng administration of both antagonists did not change the brain water content of the bilateral hemispheres.

In experiment 2, we divided the cold injured brain into cortical and deep structures, and observed the effect of the V1 receptor antagonist. Cold-injury induced signifi-cant increases in brain water and the tissue sodium con-tent of the bilateral cortical structures, but no changes in bilateral deep structures. The V₁ receptor antagonist (50 ng) significantly reduced the accumulation of water and sodium content in the cortical structures without chang-ing the plasma osmolality in any way. Five ng and 500 ng of the V₁ receptor antagonist did not in any way change the brain water content of the bilateral cortical struc-tures.

The AVP receptor antagonist inhibited the accumula-tion of water and sodium content in the cold-induced vasogenic brain edema. Of the two receptor antagonists, the V₁ receptor antagonist proved to be more effective for reducing brain edema.