Simões e Silva A C, Bello A P, Baracho N C, Khosla M C, Santos R A
Laboratório de Hipertensão, Departamento de Fisiologia e Biofísica, ICB-UFMG, Belo Horizonte, MG, Brazil.
Regul Pept. 1998 Jun 30;74(2-3):177-84. doi: 10.1016/s0167-0115(98)00038-x.
In this study we evaluated the renal effects of chronic administration of the selective Angiotensin-(1-7)[Ang-(1-7)] antagonist, A-779, in normotensive and spontaneously hypertensive rats (SHR). Male adult SHR and Wistar rats were housed in metabolic cages with tap water and standard chow, for three-five days before starting infusion (Alzet osmotic mini-pumps) of A-779 (Wistar: 1 microg/h, n = 9; 2.5 microg/h, n = 6; SHR:2.5 microg/h, n = 6) or vehicle (0.9% NaCl - 1 microl/h, n = 7 and n = 10 for SHR and Wistar rats, respectively). Urine volume, water and food intake and urinary Na+ were measured daily. On the last day of infusions mean arterial pressure (MAP) was recorded and urine and blood samples were collected to determine renal function parameters. Chronic infusion of A-779 produced a sustained increase in diuresis in normotensive rats [seventh day values: 0.75+/-0.08 ml/h (1 microg/h) and 0.94+/-0.13 ml/h (2.5 microg/h) vs. 0.42 + 0.03 ml/h for the control group, P<0.05] associated to a dose-dependent increase in the creatinine clearance. In SHR, diuresis increased significantly after chronic infusion of A-779 (fifth day values: 0.44 + 0.06 ml/h vs. 0.25+/-0.04 ml/h for the control group, P<0.05), without changes in creatinine clearance. Infusion of A-779 in normotensive rats produced a decrease in water reabsorption. A-779 infusion also produced a dose-dependent increase in urinary Na+ excretion (1.49 + 0.14 mEq, 1 microg/h vs. 2.37+/-0.22 mEq, 2.5 microg/h, P<0.05), in Wistar rats, without modifying the fractional excretion of Na+. In SHR, urinary Na+ excretion was also increased by A-779 (2.21+/-0.46 mEq vs. 0.94+/-0.22 mEq for the control group, P<0.05). No significant changes in blood pressure were observed. These findings suggest that endogenous Ang-(l-7) participates in the control of hydroelectrolyte balance by modulating water excretion, acting at tubular and glomerular sites.
在本研究中，我们评估了长期给予选择性血管紧张素 -（1 - 7）[Ang -（1 - 7）]拮抗剂A - 779对正常血压大鼠和自发性高血压大鼠（SHR）肾脏的影响。成年雄性SHR和Wistar大鼠饲养在代谢笼中，饮用自来水并给予标准饲料，在开始通过Alzet渗透微型泵输注A - 779（Wistar：1微克/小时，n = 9；2.5微克/小时，n = 6；SHR：2.5微克/小时，n = 6）或赋形剂（0.9% NaCl - 1微升/小时，SHR和Wistar大鼠分别为n = 7和n = 10）之前持续三至五天。每天测量尿量、水和食物摄入量以及尿钠。在输注的最后一天记录平均动脉压（MAP），并收集尿液和血液样本以测定肾功能参数。长期输注A - 779使正常血压大鼠的尿量持续增加[第七天的值：0.75±0.08毫升/小时（1微克/小时）和0.94±0.13毫升/小时（2.5微克/小时），而对照组为0.42 + 0.03毫升/小时，P<0.05]，同时肌酐清除率呈剂量依赖性增加。在SHR中，长期输注A - 779后尿量显著增加（第五天的值：0.44 + 0.06毫升/小时，而对照组为0.25±0.04毫升/小时，P<0.05），肌酐清除率无变化。在正常血压大鼠中输注A - 779导致水重吸收减少。在Wistar大鼠中，输注A - 779还使尿钠排泄呈剂量依赖性增加（1.49 + 0.14毫当量，1微克/小时与2.37±0.22毫当量，2.5微克/小时，P<0.05），而钠的分数排泄未改变。在SHR中，A - 779也使尿钠排泄增加（2.21±0.46毫当量，而对照组为0.94±0.22毫当量，P<0.05）。未观察到血压有显著变化。这些发现表明内源性Ang -（1 - 7）通过调节水排泄参与水电解质平衡的控制，作用于肾小管和肾小球部位。
