An enhanced effect of arginine vasopressin in bradykinin B2 receptor null mutant mice
An enhanced effect of arginine vasopressin in bradykinin B2 receptor null mutant mice
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DOI：
10.1161/01.hyp.33.6.1436
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发表时间：
1999-06-01
期刊：
影响因子：
8.3
通讯作者：
Carretero, OA
中科院分区：
文献类型：
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作者：
Alfie, ME;Alim, S;Carretero, OA
在水限制条件下，精氨酸加压素（AVP）主要通过AVP V-2受体释放并促进远端肾单位的水重吸收。我们推测激肽通过B-2受体拮抗AVP的尿浓缩作用。为了测试这一点，将缓激肽B-2受体敲除小鼠（B-2-KO）和129/SvEv小鼠（对照）置于代谢笼中并收集尿24小时（自由饮水）。之后，在限制饮水的24小时期间再次从相同小鼠收集尿。测定尿量（UV）、尿渗透压（UOsm）和尿Na+（UNaV）和K+（UKV）排泄。在限水时，对照组的UV降低了约25%，而在B-2-KO小鼠中，尿量几乎降低了60%（与对照组相比，P=0.001）。在对照组中，限水使UOsm增加了347 mOsm/kg H2O，比基线（NS）高出约14%，而在敲除小鼠中，UOsm的增加是对照组的3倍：>1000 mOsm/kg H2O（与对照组相比，P=0.001）。与正常水化相比，对照组中限水状态下的UNaV和UKV比B-2-KO小鼠增加更多。电解质排泄的这种差异可以通过对照组中更大的脱水（脱水尿钠排泄）来解释。在第二个协议中，我们试图模仿内源性AVP的作用，通过外源性施用AVP V-2受体激动剂，去氨加压素（DDAVP）。为了在DDAVP给药前抑制内源性AVP水平，用葡萄糖和酒精使小鼠体积超负荷。水负荷对照组和B-2-KO小鼠的UOsm分别为685+/-125和561+/-58 mOsm/kg H2O。皮下注射DDAVP 1 μ g/kg后，对照组UOsm增加到1175 ± 86 mOsm/kg H2O（Delta+490 mOsm），B-2-KO小鼠UOsm增加到2347 ± 518 mOsm/kg H2O（Delta+1786 mOsm）（P
Under water restriction, arginine vasopressin (AVP) is released and promotes water reabsorption in the distal nephron, mainly through AVP V-2-receptors, It has been proposed that renal kinins counteract the hydro-osmotic effect of AVP. We hypothesized that kinins acting through B-2 receptors antagonize the urinary concentrating effect of AVP. To test this, bradykinin B-2 receptor knockout mice (B-2-KO) and 129/SvEv mice (controls) were placed in metabolic cages and urine collected for 24 hours (water ad libitum), After that, urine was again collected from the same mice during 24 hours of water restriction. Urinary volume (UV), urinary osmolarity (UOsm), and urinary Na+ (UNaV) and K+ (UKV) excretion were determined. On water restriction, UV in controls decreased by approximate to 25%, whereas in B-2-KO mice there was almost a 60% drop in urinary output (P=0.001 versus controls). In the controls, water restriction increased UOsm by 347 mOsm/kg H2O, approximate to 14% above baseline (NS), whereas in knockout mice the increase was 3 times that seen in the controls: >1000 mOsm/kg H2O (P=0.001 versus controls). Compared with normohydration, UNaV and UKV in the water-restricted state increased more in controls than in B-2-KO mice. This difference in electrolyte excretion could be explained by greater dehydration in the controls (dehydration natriuresis). In a second protocol, we tried to mimic the effect of endogenous AVP by exogenous administration of an AVP V-2-receptor agonist, desmopressin (DDAVP). To suppress endogenous AVP levels before DDAVP administration, mice were volume-overloaded with dextrose and alcohol. UOsm was 685+/-125 and 561+/-58 mOsm/kg H2O in water-loaded controls and B-2-KO mice, respectively. After DDAVP was injected subcutaneously at a dose of 1 mu g/kg, UOsm increased to 1175+/-86 mOsm/kg H2O (Delta+490 mOsm) in the controls and 2347+/-518 mOsm/kg H2O (Delta+1786 mOsm) in B-2-KO mice (P