Cox S L, Trendelenburg A U, Starke K
Pharmakologisches Institut, Freiburg University, Germany.
Br J Pharmacol. 1999 Jul;127(5):1256-62. doi: 10.1038/sj.bjp.0702652.
The effect of angiotensin II, angiotensin III, angiotensin IV and angiotensin-(1-7) on the electrically induced release of noradrenaline was studied in preparations of mouse atria, spleen, hippocampus, occipito-parietal cortex and hypothalamus preincubated with [3H]-noradrenaline. The prejunctional angiotensin receptor type was investigated using the non-selective receptor antagonist saralasin (AT1/AT2) and the AT1 and AT2 selective receptor antagonists losartan and PD 123319, respectively. In atrial and splenic preparations, angiotensin II (0.01 nM-0.1 microM) and angiotensin III (0.01 and 0.1 nM-1 microM) increased the stimulation-induced overflow of tritium in a concentration-dependent manner. Angiotensin IV, only at high concentrations (1 and 10 pM), enhanced tritium overflow in the atria, while angiotensin-(1-7) (0.1 nM-10 microM) was without effect in both preparations. In preparations of hippocampus, occipito-parietal cortex and hypothalamus, none of the angiotensin peptides altered the evoked overflow of tritium. In atrial and splenic preparations, saralasin (0.1 microM) and losartan (0.1 and 1 microM), but not PD 123319 (0.1 microM), shifted the concentration-response curves of angiotensin II and angiotensin III to the right. In conclusion, in mouse atria and spleen, angiotensin II and angiotensin III facilitate the action potential induced release of noradrenaline via a prejunctional AT1 receptor. Only high concentrations of angiotensin IV are effective in the atria and angiotensin-(1-7) is without effect in both preparations. In mouse brain areas, angiotensin II, angiotensin III, angiotensin IV and angiotensin-(1-7) do not modulate the release of noradrenaline.
在预先用[3H]-去甲肾上腺素孵育的小鼠心房、脾脏、海马、枕顶叶皮质和下丘脑标本中,研究了血管紧张素II、血管紧张素III、血管紧张素IV和血管紧张素-(1 - 7)对电诱导的去甲肾上腺素释放的影响。使用非选择性受体拮抗剂沙拉新(AT1/AT2)以及分别为AT1和AT2选择性受体拮抗剂的氯沙坦和PD 123319来研究接头前血管紧张素受体类型。在心房和脾脏标本中,血管紧张素II(0.01 nM - 0.1 microM)和血管紧张素III(0.01和0.1 nM - 1 microM)以浓度依赖性方式增加刺激诱导的氚溢出。血管紧张素IV仅在高浓度(1和10 pM)时增强心房中的氚溢出,而血管紧张素-(1 - 7)(0.1 nM - 10 microM)在两种标本中均无作用。在海马、枕顶叶皮质和下丘脑标本中,没有一种血管紧张素肽改变诱发的氚溢出。在心房和脾脏标本中,沙拉新(0.1 microM)和氯沙坦(0.1和1 microM),但不是PD 123319(0.1 microM),将血管紧张素II和血管紧张素III的浓度 - 反应曲线向右移动。总之,在小鼠心房和脾脏中,血管紧张素II和血管紧张素III通过接头前AT1受体促进动作电位诱导的去甲肾上腺素释放。只有高浓度的血管紧张素IV在心房中有效,而血管紧张素-(1 - 7)在两种标本中均无作用。在小鼠脑区中,血管紧张素II、血管紧张素III、血管紧张素IV和血管紧张素-(1 - 7)不调节去甲肾上腺素的释放。