Ferreira-do-Vale C, Renzi A, Camargo G P, Saad W A, Luiz A C, Menani J V, Silveira J E, Camargo L A
Departamento de Ciências Fisiológicas, Faculdade de Odontologia, Universidade Estadual Paulista, Araraquara, SP, Brasil.
Braz J Med Biol Res. 1995 Oct;28(10):1097-101.
We determined the effects of two classical angiotensin II (ANG II) antagonists, [Sar1, Ala8]-ANG II and [Sar1, Thr8]-ANG II, and losartan (a nonpeptide and selective antagonist for the AT1 angiotensin receptors) on diuresis, natriuresis, kaliuresis and arterial blood pressure induced by ANG II administration into the median preoptic nucleus (MnPO) of male Holtzman rats weighing 250-300 g. Urine was collected in rats submitted to a water load (5% body weight) 1 h later. The volume of the drug solutions injected was 0.5 microliters over 10-15 s. Pre-treatment with [Sar1, Ala8]-ANG II (12 rats) and [Sar1, Thr8]-ANG II (9 rats), at the dose of 60 ng reduced (13.7 +/- 1.0 vs 11.0 +/0 1.0 and 10.7 +/0 1.2, respectively), whereas losartan (14 rats) at the dose of 160 ng totally blocked (13.7 +/- 1.0 vs 7.6 +/- 1.5) the urine excretion induced by injection o 12 ng of ANG II (14 rats). [Sar1, Ala8]-ANG II impaired Na+ excretion (193 +/- 16 vs 120 +/- 19), whereas [Sar1, Thr8]-ANG II and losartan block Na+ excretion (193 +/- 16 vs 77 +/- 15 and 100 +/- 12, respectively) induced by ANG II. Similar effects induced by ANG II on K+ excretion were observed with [Sar1, Ala8]-ANG II, [Sar1, Thr8]- ANG II, and losartan pretreatment (133 +/- 18 vs 108 +/- 11, 80 +/- 12, and 82 +/- 15, respectively). The same doses as above of [Sar1, Ala8]-ANG II (8 rats), [Sar1, Thr8]-ANG II (8 rats), and losartan (9 rats) blocked the increase in the arterial blood pressure induced by 12 ng of ANG II (12 rats) (32 +/- 4 vs 4 +/- 2, 3.5 +/- 1, and 2 +/- 1, respectively. The results indicate that the AT1 receptor subtype participates in the increases of diuresis, natriuresis, kaliuresis and arterial blood pressure induced by the administration of ANG II into the MnPO.
我们研究了两种经典的血管紧张素II（ANG II）拮抗剂，即[Sar1, Ala8]-ANG II和[Sar1, Thr8]-ANG II，以及氯沙坦（一种非肽类且对AT1血管紧张素受体具有选择性的拮抗剂），对体重250 - 300克的雄性霍尔茨曼大鼠中视前核（MnPO）注射ANG II所诱导的利尿、利钠、利钾及动脉血压的影响。1小时后，对接受水负荷（体重的5%）的大鼠收集尿液。在10 - 15秒内注射的药物溶液体积为0.5微升。用剂量为60纳克的[Sar1, Ala8]-ANG II（12只大鼠）和[Sar1, Thr8]-ANG II（9只大鼠）预处理可减少尿量（分别为13.7±1.0对11.0±1.0和10.7±1.2），而剂量为160纳克的氯沙坦（14只大鼠）可完全阻断注射12纳克ANG II（14只大鼠）所诱导的尿排泄（13.7±1.0对7.6±1.5）。[Sar1, Ala8]-ANG II损害Na⁺排泄（193±16对120±19），而[Sar1, Thr8]-ANG II和氯沙坦可阻断ANG II诱导的Na⁺排泄（分别为193±16对77±15和100±12）。用[Sar1, Ala8]-ANG II、[Sar1, Thr8]-ANG II和氯沙坦预处理时，观察到ANG II对K⁺排泄有类似影响（分别为133±18对108±11、80±12和82±15）。上述相同剂量的[Sar1, Ala8]-ANG II（8只大鼠）、[Sar1, Thr8]-ANG II（8只大鼠）和氯沙坦（9只大鼠）可阻断12纳克ANG II（12只大鼠）所诱导的动脉血压升高（分别为32±4对4±2、3.5±1和2±1）。结果表明，AT1受体亚型参与了向MnPO注射ANG II所诱导的利尿、利钠、利钾及动脉血压升高过程。
