Alzamora A C, Santos R A S, Campagnole-Santos M J
Departamento de Fisiologia e Biofísica, Instituto de Ciências Biológicas Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
Am J Physiol Regul Integr Comp Physiol. 2002 Nov;283(5):R1187-95. doi: 10.1152/ajpregu.00580.2001.
The objective of the present study was to determine the contribution of the autonomic nervous system and nitric oxide to the depressor effect produced by unilateral microinjection of ANG-(1-7) and ANG II into the caudal ventrolateral medulla (CVLM). Unilateral microinjection of ANG-(1-7), ANG II (40 pmol), or saline (100 nl) was made into the CVLM of male Wistar rats anesthetized with urethane before and after intravenous injection of 1) methyl-atropine, 2.5 mg/kg; 2) prazosin, 25 microg/kg; 3) the nitric oxide synthase (NOS) inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME), 5 mg/kg; or 4) the specific inhibitor of neuronal NOS, 7-nitroindazole (7-NI), 45 mg/kg. Arterial pressure and heart rate (HR) were continuously monitored. Microinjection of ANG-(1-7) or ANG II into the CVLM produced a significant decrease in mean arterial pressure (MAP; -11 +/- 1 mmHg, n = 12 and -10 +/- 1 mmHg, n = 10, respectively) that was not accompanied by consistent changes in HR or in cardiac output. The effect of ANG-(1-7) was abolished after treatment with methyl-atropine (-3 +/- 0.6 mmHg, n = 9) or L-NAME (-2.3 +/- 0.5 mmHg, n = 8) or 7-NI (-2.8 +/- 0.6 mmHg, n = 5). In contrast, these treatments did not significantly interfere with the ANG II effect (-10 +/- 2.6 mmHg, n = 8; -8 +/- 1.5 mmHg, n = 8; and -12 +/- 3.6 mmHg, n = 6; respectively). Peripheral treatment with prazosin abolished the hypotensive effect of ANG-(1-7) and ANG II. Microinjection of saline did not produce any significant change in MAP or in HR. These results suggest that the hypotensive effect produced by ANG II at the CVLM depends on changes in adrenergic vascular tonus and, more importantly, the hypotensive effect produced by ANG-(1-7) also involves a nitric oxide-related mechanism.
本研究的目的是确定自主神经系统和一氧化氮对尾侧腹外侧延髓（CVLM）单侧微量注射血管紧张素 -（1 - 7）[ANG -（1 - 7）]和血管紧张素II（ANG II）所产生的降压作用的贡献。在静脉注射以下药物之前和之后，将ANG -（1 - 7）、ANG II（40 pmol）或生理盐水（100 nl）单侧微量注射到用乌拉坦麻醉的雄性Wistar大鼠的CVLM中：1）甲基阿托品，2.5 mg/kg；2）哌唑嗪，25 μg/kg；3）一氧化氮合酶（NOS）抑制剂，N（G）-硝基 - L -精氨酸甲酯（L - NAME），5 mg/kg；或4）神经元NOS的特异性抑制剂，7 - 硝基吲唑（7 - NI），45 mg/kg。持续监测动脉血压和心率（HR）。向CVLM微量注射ANG -（1 - 7）或ANG II可使平均动脉压（MAP）显著降低（分别为-11±1 mmHg，n = 12和-10±1 mmHg，n = 10），且心率或心输出量无一致变化。用甲基阿托品（-3±0.6 mmHg，n = 9）、L - NAME（-2.3±0.5 mmHg，n = 8）或7 - NI（-2.8±0.6 mmHg，n = 5）处理后，ANG -（1 - 7）的作用消失。相比之下，这些处理并未显著干扰ANG II的作用（分别为-10±2.6 mmHg，n = 8；-8±1.5 mmHg，n = 8；和-12±3.6 mmHg，n = 6）。用哌唑嗪进行外周处理可消除ANG -（1 - 7）和ANG II的降压作用。微量注射生理盐水对MAP或HR无任何显著影响。这些结果表明，ANG II在CVLM产生的降压作用取决于肾上腺素能血管紧张度的变化，更重要的是，ANG -（1 - 7）产生的降压作用还涉及一种与一氧化氮相关的机制。
