|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.