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循环中的钠钾ATP酶抑制剂:神经肽、容量扩张和盐负荷对清醒大鼠的影响

Circulating Na+/K+-ATPase inhibitors: effects of neuropeptides, volume expansion and salt loading in conscious rats.

作者信息

Schmitt B M, Unger T, Rettig R

机构信息

Department of Pharmacology, University of Heidelberg, Germany.

出版信息

Clin Exp Pharmacol Physiol. 1997 Feb;24(2):131-8. doi: 10.1111/j.1440-1681.1997.tb01795.x.

DOI:10.1111/j.1440-1681.1997.tb01795.x
PMID:9075584
Abstract
  1. In mammalian plasma, many different inhibitors of Na+/K(+)-ATPase are present, but it is not clear whether their net effect on NA+/K(+)-ATPase activity changes during the regulation of electrolyte and fluid balance. We studied Na+/K(+)-ATPase inhibition by plasma extracts in conscious rats during short- and long-term body fluid regulation. 2. Male, adult, conscious, freely moving Wistar rats were subjected to one of the following protocols: (i) intracerebro-ventricular (i.c.v.) injections of angiotension II (AngII; 1, 10 and 100 ng), the AngII receptor antagonist losartan (1 microgram), atrial natriuretic peptide (ANP-III; 1 microgram) or isotonic saline (IS); (ii) intra-arterial (i.a.) injections of IS (6 or 10 mL), hypertonic saline (HS; 1.2% NaCl, 5 mL) or hypertonic plasma expander (HPS; 3.5% hetastarch in HS, 5 mL); or (iii) a low salt-high salt-low salt diet sequence (0.18/1.8/0.18% NaCl chow for 5 days each with controls receiving 0.18% NaCl on all days). Bodyweight, the intake of food and water, urine volume and Na+ concentration and weight of faeces were determined daily. Plasma samples were withdrawn repeatedly throughout the respective protocols, extracted on C18-reversed phase columns and assayed for their effect on the activity of different Na+/K(+)-ATPase preparations. 3. The inhibition of rat brain Na+/K(+)-ATPase by plasma extracts was not significantly changed by i.c.v. injection of AngII, losartan, ANP-III and IS within the observation period (30 min from respective stimuli). Similarly, no significant changes occurred after acute volume expansion by i.a. injection of IS or HS within 120 min; upon HPS, however, Na+/K(+)-ATPase inhibition was decreased by approximately 20% (P < 0.05), probably due to passive dilution. During the high-salt diet, fluid retention was effectively counteracted by an adaptive increase of urinary sodium excretion. Throughout the protocol, inhibition of pig brain Na+/K(+)-ATPase by plasma extracts did not differ significantly between groups. 4. It is concluded from these results that the short- or long-term control of body fluids in conscious rats is not associated with systematic changes in Na+/K(+)-ATPase inhibition by plasma factors.
摘要
  1. 在哺乳动物血浆中存在许多不同的钠钾ATP酶抑制剂,但在电解质和体液平衡调节过程中,它们对钠钾ATP酶活性的净效应是否改变尚不清楚。我们研究了清醒大鼠在短期和长期体液调节过程中血浆提取物对钠钾ATP酶的抑制作用。2. 成年雄性清醒自由活动的Wistar大鼠接受以下方案之一:(i)脑室内注射血管紧张素II(AngII;1、10和100纳克)、AngII受体拮抗剂氯沙坦(1微克)、心房利钠肽(ANP-III;1微克)或等渗盐水(IS);(ii)动脉内注射IS(6或10毫升)、高渗盐水(HS;1.2%氯化钠,5毫升)或高渗血浆扩容剂(HPS;3.5%羟乙基淀粉于HS中,5毫升);或(iii)低盐-高盐-低盐饮食序列(0.18/1.8/0.18%氯化钠饲料,各5天,对照组每天接受0.18%氯化钠)。每天测定体重、食物和水摄入量、尿量、钠浓度及粪便重量。在各个方案过程中反复采集血浆样本,在C18反相柱上进行提取,并测定其对不同钠钾ATP酶制剂活性的影响。3. 在观察期内(各刺激后30分钟),脑室内注射AngII、氯沙坦、ANP-III和IS对血浆提取物抑制大鼠脑钠钾ATP酶的作用无显著改变。同样,动脉内注射IS或HS在120分钟内急性扩容后也无显著变化;然而,注射HPS后,钠钾ATP酶抑制作用降低约20%(P<0.05),可能是由于被动稀释。在高盐饮食期间,尿钠排泄的适应性增加有效抵消了液体潴留。在整个方案过程中,各组间血浆提取物对猪脑钠钾ATP酶的抑制作用无显著差异。4. 从这些结果得出结论,清醒大鼠的短期或长期体液控制与血浆因子对钠钾ATP酶抑制作用的系统性变化无关。

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