Hassan S, Mori M, Obara H
Department of Anesthesiology, Kobe University School of Medicine.
Kobe J Med Sci. 1996 Feb;42(1):73-91.
The present study was designed to compare the in vitro vasorelaxant responses to the bipyridine compound amrinone of prostaglandin F2 alpha (PGF2 alpha) precontracted aortic strips isolated from newborn (2 to 3 days old) and nonpregnant adult rabbits. Changes in forces were recorded isometrically. The effects of isoproterenol (beta-adrenergic receptor stimulator), forskolin (direct activator of adenylate cyclase) and theophylline (non-specific phosphodiesterase inhibitor) were also studied simultaneously. The vasodilator responses to amrinone, forskolin and theophylline in aortic strips from neonates were comparable to those of strips from adults. In contrast, the maximum relaxations to isoproterenol were significantly reduced in those from neonates as compared with those from adults, suggesting that beta-adrenergic receptor mediated responses are not fully developed in the neonate. The mean value for the ED50 concentration (half the maximum response) for amrinone, isoproterenol and theophylline was 1.10 +/- 0.10 x 10(-4) M, 3.47 +/- 1.31 x 10(-8) M and 1.53 +/- 0.10 x 10(-4) M, respectively, in the neonatal group and 1.17 +/- 0.19 x 10(-4) M, 3.75 +/- 1.11 x 10(-8) M and 1.75 +/- 0.06 x 10(-4) M, respectively, in the adult group; there were no significant differences between the neonatal and adult preparations. We concluded that the vasorelaxation produced by phosphodiesterase inhibitors demonstrated no maturation-related changes probably due to a stable cyclic AMP turnover through an unaltered phosphodiesterase activity in newborn and adult arteries.
本研究旨在比较前列腺素F2α(PGF2α)预收缩的新生(2至3日龄)和未孕成年兔离体主动脉条对双吡啶化合物氨力农的体外血管舒张反应。等长记录力量变化。同时还研究了异丙肾上腺素(β-肾上腺素能受体刺激剂)、福斯高林(腺苷酸环化酶直接激活剂)和茶碱(非特异性磷酸二酯酶抑制剂)的作用。新生兔主动脉条对氨力农、福斯高林和茶碱的血管舒张反应与成年兔主动脉条相当。相比之下,与成年兔相比,新生兔主动脉条对异丙肾上腺素的最大舒张反应明显降低,这表明新生儿中β-肾上腺素能受体介导的反应尚未完全发育。氨力农、异丙肾上腺素和茶碱的ED50浓度(最大反应的一半)平均值在新生组分别为1.10±0.10×10⁻⁴ M、3.47±1.31×10⁻⁸ M和1.53±0.10×10⁻⁴ M,在成年组分别为1.17±0.19×10⁻⁴ M、3.75±1.11×10⁻⁸ M和1.75±0.06×10⁻⁴ M;新生组和成年组制剂之间无显著差异。我们得出结论,磷酸二酯酶抑制剂产生的血管舒张作用未显示出与成熟相关的变化,这可能是由于新生和成年动脉中磷酸二酯酶活性未改变,环磷酸腺苷周转稳定所致。