高血圧心の肥大および冠循環障害におけるAngiotensin IIの役割

The Role of Angiotensin II in Hypertensive Cardiac Hypertrophy and Impaired Coronary Circulation

　高血圧心の冠循環障害の機序に占めるレニン—アンジオテンシン系の役割と圧負荷の関与につき検討するため，DOCA食塩高血圧ラットにアンジオテンシンII受容体拮抗薬（TCV-116）を投与した．TCV-116の投与期間中，高血圧は持続した．8週後，摘出心をLangen-dorff灌流にて定量灌流を行い冠灌流抵抗を算出，左室重量も測定した．DOCA＋TCV群はDOCA群より心重量の軽減を認め，レニン—アンジオテンシン系抑制は降圧なくとも心肥大退縮に関与すると考えられた．DOCA＋TCV群はDOCA群と比較し最小冠血管抵抗値は有意に低下しており，DOCA食塩負荷高血圧ラットにおける冠循環障害をアンジオテンシンII受容体拮抗薬（TCV-116）は心肥大退縮とともに改善した．L-NMMA灌流液中への投与はすべての群で冠血管抵抗を上昇させるも，群間に有意差は認められなかった．DOCA高血圧ラットにおける肥大心では，肥大と冠循環障害の発現にアンジオテンシン系の関与が示唆された．さらにこの冠循環障害に冠血管のNO産生の関与は少ないことが示唆された．

Hypertensive rats were produced by the treatment of deoxycorticosterone acetates (DOCA) with 8% NaC1 diet and sham-operated rats were used for control. They were divided into two groups. In one group. Ang II receptor antagonist (TCV-116) was administrated for 8 weeks. Rat's heart was isolated and placed to Langen-dorff apparatus perfusing at a constant flow of 12ml/ min. To obtain maximal coronary dilation. adenosine (10^-5M) was infused. And heart was perfused with NO inhibitor, L-NMMA (10^-4M) to examine the role of EDRF. At the end of experiment, left ventricle were weighed. At 4 weeks treatment of DOCA, the hyperten-sive cardiac hypertrophy was produced. TCV-116 reduced cardiac hypertrophy without antihypertensive effect in DOCA rats. Simultaneously. TCV-116 reduced the increased minimal coronary vascular resistance in DOCA rats. L-NMMA incrased coronary vascular resistance in all rats with same manner. The improve-ment of coronary circulation by TCV-116 was conclud-ed to be independent from EDRF.