Weiss D N, Podberesky D J, Heidrich J, Blaustein M P
Department of Physiology, University of Maryland School of Medicine, Baltimore 21201.
Am J Physiol. 1993 Nov;265(5 Pt 1):C1443-8. doi: 10.1152/ajpcell.1993.265.5.C1443.
Chronic parenteral administration of ouabain to normal rats raises plasma ouabain concentrations to low nanomolar levels and induces hypertension [C. M. Yuan, P. Manunta, J. M. Hamlyn, S. W. Chen, E. Bohen, J. Yeun, F. J. Haddy, and M. B. Pamnani. Hypertension 22: 178-187, 1993 and see also M. P. Blaustein. Am. J. Physiol. 264 (Cell Physiol. 33): C1367-C1387, 1993]. To determine whether rat arteries are sensitive to these low ouabain levels, we tested the effects of various ouabain concentrations on caffeine-evoked contractions (CEC) in rat aortic and small mesenteric artery rings. CEC amplitude was used as a measure of the sarcoplasmic reticulum (SR) Ca2+ content. Ouabain increased CEC in aortic as well as mesenteric artery rings, but the effects in the aorta were difficult to quantitate because the CEC were often oscillatory. Mesenteric artery, under control conditions and after sensitization with 10-30 nM phenylephrine (PE), exhibited biphasic ouabain dose-CEC response curves. Low concentrations of ouabain (0.1-10 nM) caused small significant increases in CEC, but a further effect was observed only with > or = 10 microM ouabain. PE shifted the ouabain dose-response curve toward lower ouabain concentrations; conversely, ouabain shifted the PE dose-response curve toward lower PE concentrations. It appears that nanomolar concentrations of ouabain can influence vascular responsiveness to vasoconstrictors. We conclude that rat vascular smooth muscle contains both high- and low-affinity ouabain receptors, possibly corresponding to Na+ pumps with alpha 3- and alpha 1-subunit isoforms, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
对正常大鼠长期进行哇巴因的肠胃外给药会使血浆哇巴因浓度升高至低纳摩尔水平，并诱发高血压[C.M.袁、P.马努塔、J.M.哈姆林、S.W.陈、E.博恩、J.云、F.J.哈迪和M.B.帕姆纳尼。《高血压》22: 178 - 187，1993年，另见M.P.布劳斯坦。《美国生理学杂志》264(细胞生理学33): C-1367 - C-1387，1993年]。为了确定大鼠动脉是否对这些低哇巴因水平敏感，我们测试了不同哇巴因浓度对大鼠主动脉和小肠系膜动脉环中咖啡因诱发收缩(CEC)的影响。CEC幅度被用作肌浆网(SR)钙含量的指标。哇巴因增加了主动脉以及肠系膜动脉环中的CEC，但在主动脉中的影响难以定量，因为CEC常常呈振荡性。在对照条件下以及用10 - 30纳摩尔去甲肾上腺素(PE)致敏后，肠系膜动脉呈现出双相的哇巴因剂量 - CEC反应曲线。低浓度的哇巴因(0.1 - 10纳摩尔)使CEC有小幅显著增加，但仅在哇巴因浓度≥10微摩尔时才观察到进一步的效应。PE使哇巴因剂量 - 反应曲线向更低的哇巴因浓度方向移动；相反，哇巴因使PE剂量 - 反应曲线向更低的PE浓度方向移动。看来纳摩尔浓度的哇巴因能够影响血管对血管收缩剂的反应性。我们得出结论，大鼠血管平滑肌含有高亲和力和低亲和力的哇巴因受体，可能分别对应于具有α3和α1亚基异构体的钠泵。(摘要截短于250词)
