|Budget Amount *help
¥4,000,000 (Direct Cost : ¥4,000,000)
Fiscal Year 1998 : ¥300,000 (Direct Cost : ¥300,000)
Fiscal Year 1997 : ¥3,700,000 (Direct Cost : ¥3,700,000)
Angiotensin 3-8 (Ang 3-8) is one of the metabolites of angiotensinogen. Ang 3-8 has unique physiological activities, which are different from those of angiotensin II (All). Kidney is one of the organs rich, in angiotensinogen metabolites. We examined the direct action of angiotensin 3-8 on isolated microperfused rabbit afferent arterioles (Af-Art) and whether endothelium-derived nitric oxide (EDNO) and angiotensin II type 1 (AT1) receptors are involved in its action from New Zealand White Rabbits. Af-Arts with the glomerulus intact was microdissected from the superficial cortex of kidneys and perfused in vitro at the pressure of 60mmHg. The luminal diameter of Af-Arts was determined using a video measuring system. The diameter of Af-Arts decreased in the presence of Ang 3-8 in a dose-dependent manner. To attain the same effect caused by AII, the concentration of Ang 3-8 has to be thousand times higher than that of AII.This constriction was completely blocked by CV11974, an AT1 receptor
antagonist. On the other hand, the luminal diameter of Af-Art preconstricted with norepinephrine (NE) by Ang 3-8, as increased in the presence of NE.The basal luminal diameter decreased from 16.5*0.9 to 12.9*0.6 mum. (n = 7). Maximal dilation [15.2*0.6 mum (n=7)] was obtained with Ang 3-8, at 10- 6mol/L.This dilatation was abolished by inhibiting EDNO with 10<@D1-4@>D1mol/L N<@D1w@>D1-nitro-L-arginine methyl ester (L-NAME). After treatment with L-NAME, Ang 3-8 did not produce dilation, but the diameter rather tended to decrease even further to 12.2*0.8, 10 7*0.9 and 6.6*1.4 mum, at 10<@D1-7@>D1, 10<@D1-6@>D1 and 10<@D1-5@>D1 mol/L, respectively (p(]SY.di-substituted right.[)O.O5, n = 7). We conclude that at high concentrations Ang 3-8 constricts isolated microperfused rabbit afferent arterioles via the ATI receptor while at low concentrations of it has a partial vasodilator action mediated via endothelium derived releasing factor.
腎糸球体輸入細動脈上のアシジオテンシン受容体の血管収縮反応に関与するアンジオテンシンII ATl、AT2レセプターの作用を以下の方法で検討した。New Zealand White Rabbitの左腎を摘出、実体顕微鏡下に腎皮質より単一のAf-Artを糸球体が付着した状態で単離した。MEM液にて60mmHgで定圧灌流し、以下の実験を行った。10^<-8>MアンジオテンシンIIによる前収縮後、10^<-7>〜10^<-5>Mの選択的AT1レセプター阻害薬であるCV11974、AT2阻害薬であるPD123319を各々灌流槽に加えAf-Artにおける用量反応曲線をみた。アンジオテンシンIIは容量依存性にAf-Artを収縮させた。この収縮反応をCV11974は容量依存性に抑制した(10.0±0.80,11.8±0.86,13.1±0.73μm,n=7)。PDl23319は抑制しなかった(11.9±1.81,11.5±2.05,11.1±2.15μm,n=7)。以上よりアンジオテンシンIIはAf-ArtにおいてAT1レセプターを介して収縮させた。この収縮反応に関してはAT2レセプターは関与していなかった。 Less