Shimakura K, Sanaka M, Wang L, Mineshita S, Miyazaki M
Department of Preventive Medicine, Medical Research Institute, Tokyo Medical and Dental University, Japan.
Jpn J Pharmacol. 1995 Apr;67(4):383-9. doi: 10.1254/jjp.67.383.
We performed this study to demonstrate the experimental procedure for inducing pulmonary edema by angiotensin II (AT II) in rats and to determine the mechanism of hemodynamic pulmonary edema. In the pilot study, 10 micrograms/ml of AT II was found to be adequate as the edematogenic dose for inducing pulmonary edema. The edematogenic dose of AT II was intravenously given to rats pretreated with 20 mg/kg of an AT II-receptor antagonist, E 4177 (3-[(2'-carboxybiphenyl-4-yl)methyl]-2-cyclopropyl-7-methyl-3H- imidazo[4,5-b]pyridine), and to rats given 10 mg/kg of an alpha-adrenergic blocker, phentolamine. Similarly, pulmonary edema was induced by 25 micrograms/ml of adrenaline in rats pretreated with E 4177 (20 mg/kg) and rats with no pretreatment. E 4177 completely suppressed the development of AT II-induced pulmonary edema, whereas phentolamine could not. On the contrary, E 4177 could not suppress the development of adrenaline-induced pulmonary edema. We concluded that AT II-induced pulmonary edema will develop via the specific AT II receptor without the indirect action of adrenaline.
我们进行这项研究以证明在大鼠中通过血管紧张素II(AT II)诱导肺水肿的实验程序,并确定血流动力学性肺水肿的机制。在预实验中,发现10微克/毫升的AT II作为诱导肺水肿的致水肿剂量是足够的。将AT II的致水肿剂量静脉注射给用20毫克/千克的AT II受体拮抗剂E 4177(3-[(2'-羧基联苯-4-基)甲基]-2-环丙基-7-甲基-3H-咪唑并[4,5-b]吡啶)预处理的大鼠,以及给予10毫克/千克α-肾上腺素能阻滞剂酚妥拉明的大鼠。同样,用E 4177(20毫克/千克)预处理的大鼠和未预处理的大鼠通过25微克/毫升的肾上腺素诱导肺水肿。E 4177完全抑制了AT II诱导的肺水肿的发展,而酚妥拉明则不能。相反,E 4177不能抑制肾上腺素诱导的肺水肿的发展。我们得出结论,AT II诱导的肺水肿将通过特异性AT II受体发展,而无需肾上腺素的间接作用。