EFFECT OF VASOPRESSIN ANTAGONIST ON WATER-EXCRETION IN INFERIOR VENA-CAVA CONSTRICTION
EFFECT OF VASOPRESSIN ANTAGONIST ON WATER-EXCRETION IN INFERIOR VENA-CAVA CONSTRICTION
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DOI：
10.1038/ki.1986.149
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发表时间：
1986-07-01
影响因子：
19.6
通讯作者：
KUZUYA, T
中科院分区：
文献类型：
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作者：
ISHIKAWA, S;SAITO, T;KUZUYA, T
血浆精氨酸加压素（AVP）水平升高已被认为是损害充血性心力衰竭的水分排泄。在本研究中，以确定AVP在受损的水排泄与下腔静脉狭窄（IVC）的大鼠中的作用，两个AVP拮抗剂在IVC大鼠在近端部分的肝静脉下的隔膜和假手术（对照）大鼠。手术后，在实验开始前允许48小时。平均心脏指数为260.0 ±。12.3 IVC大鼠中的323.6 ± 0.5ml/min/kg显著低于对照大鼠。13.2 ml/min/kg（P < 0.01）。给予大鼠抗利尿剂拮抗剂[1-（β-巯基-β，β-环戊亚甲基丙酸）、2-（O-乙基）-D-酪氨酸、4-缬氨酸] AVP（30 μ g/kg）或拮抗剂载体，腹膜内，20分钟后口服30 ml/kg水。接受载体的IVC大鼠中的最小尿渗透压（Uosm）显著大于对照大鼠（292.7 ± 0.01）。53.1与97.8 .+-相比。10.6 mOsm/kg H2O，P < 0.01）。在IVC大鼠中施用抗利尿剂拮抗剂使最小Uosm降低至90.0 ±。3.6 mOsm/kg H2O。该值显著低于载体大鼠（P < 0.01），并且与最小Uosm 82.1 ±-相当。3.7接受抗利尿剂拮抗剂的对照大鼠中的mOsm/kg H2O。IVC大鼠排泄51.4 ±。在3小时内排泄水负荷的5.9%，该值显著低于对照大鼠排泄的值95.1 ± 0.9%。6.0%（P < 0.01）。当用抗利尿剂拮抗剂治疗时，排泄的水负荷的百分比增加到143.7 . ±. IVC大鼠为9.4%。抗利尿剂拮抗剂的疗效与不可抑制的血浆AVP水平相关。血浆AVP水平为2.1 ± 0.01。0.6在IVC大鼠中，通过给予水不能充分抑制pg/ml，这诱导了低渗透压。与此相反，在对照大鼠中，血浆AVP降低至0.7 ± 0.5。0.2 pg/ml，在相同的情况下。然而，升高的AVP对血压的维持没有贡献，因为血管加压素拮抗剂[1-（β-AVP）]巯基-β，β-环戊亚甲基丙酸），2-（O-甲基）-酪氨酸] AVP，不影响平均动脉压。因此，这些结果表明，AVP的非渗透释放不适当地增加，从而损害IVC大鼠的肾脏水分排泄，并且预期抗利尿剂拮抗剂在这种状态下具有生物学功效。
Elevated levels of plasma arginine vasopressin (AVP) have been suggested to impair water excretion in congestive heart failure. In the present study, to determine a role for AVP in the impaired water excretion in rats with the inferior vena cava constriction (IVC), two AVP antagonists were used in the IVC rats at the proximal portion of the hepatic vein under the diaphragm and in sham-operated (control) rats. After surgery, 48 hrs were allowed before the experiments were started. A mean cardiac index of 260.0 .+-. 12.3 ml/min/kg in the IVC rats was significantly lower than that in the control rats, 323.6 .+-. 13.2 ml/min/kg (P < 0.01). The rats were given an antidiuretic antagonist, [1-(.beta.-mercapto-.beta., .beta.-cyclopentamethylenepropionic acid), 2-(O-ethyl)-D-tyrosine, 4-valine] AVP (30 .mu.g/kg) or the antagonist vehicle, i.p., and 20 min later they were administered 30 ml/kg of water orally. Minimal urinary osmolality (Uosm) in the IVC rats receiving the vehicle was significantly greater than the control rats (292.7 .+-. 53.1 vs. 97.8 .+-. 10.6 mOsm/kg H2O, P < 0.01). The administration of the antidiuretic antagonist in the IVC rats decreased minimal Uosm to 90.0 .+-. 3.6 mOsm/kg H2O. This value was significantly lower than the vehicle rats (P < 0.01), and was a comparable level to minimal Uosm of 82.1 .+-. 3.7 mOsm/kg H2O in the control rats receiving the antidiuretic antagonist. The IVC rats excreted 51.4 .+-. 5.9% of the water load in three hr, a value significantly less than that excreted by the control rats, 95.1 .+-. 6.0% (P < 0.01). When treated with the antidiuretic antagonist, the percent of water load excreted increased to 143.7 .+-. 9.4% in the IVC rats. The efficacy of the antidiuretic antagonist was associated with nonsuppressible plasma AVP levels. The plasma AVP level of 2.1 .+-. 0.6 pg/ml was not sufficiently suppressed in the IVC rats by the administration of water, which induced hypoosmolality. In contrast, in the control rats plasma AVP was decreased to 0.7 .+-. 0.2 pg/ml in the same situation. However, the elevated AVP did not contribute to the maintenance of blood pressure since the vasopressor antagonist, [1-(.beta.-mercapto-.beta., .beta.-cyclopentamethylenepropionic acid), 2-(O-methyl)-tyrosine] AVP, did not affect mean arterial pressure. These results therefore indicate that the non-osmotic release of AVP is inappropriately increased to impair renal water excretion in the IVC rats and the biological efficacy of the antidiuretic antagonist in such a state is expected.