Kohlmann O, Gavras I, Biollaz J, Biollaz B, Gavras H
J Hypertens. 1985 Jun;3(3):269-74. doi: 10.1097/00004872-198506000-00012.
Recent research has demonstrated that sodium diminishes the affinity of alpha 2-adrenoceptors for agonists in vitro. Clonidine, a highly specific agonist for alpha 2-receptors, has a transient hypertensive effect when administered parenterally. We studied in conscious anephric Wistar rats the effect of equimolar saline or mannitol solutions on the hypertensive response to clonidine administered subcutaneously in doses of 10, 100 and 1000 micrograms/kg body weight. Prior saline infusion reduced the hypertensive response to the two higher doses of clonidine by 65 and 70%, and displaced the slope of the dose-response curve downwards, but mannitol had no such effect. Pre-treatment with the alpha 2-antagonist yohimbine abolished the differences in clonidine-induced pressor response between saline-treated, mannitol-treated and control rats. On the contrary, after pre-treatment with the alpha 1-antagonist prazosin, the pressor action of clonidine was significantly reduced in the saline-infused rats compared to the other two groups. Thus the saline-induced blunting of the pressor response elicited by clonidine could be negated by prior alpha 2- but not alpha 1-blockade, indicating that sodium interfered with the stimulation of post-synaptic vascular alpha 2-adrenoceptors. These findings indicate that loading with sodium chloride attenuates the alpha 2-adrenoceptor function in vivo. Based on this, we suggest that the mechanism by which sodium excess causes a rise in blood pressure involves modification of the alpha 2-adrenoceptors.
近期研究表明，在体外，钠会降低α2-肾上腺素能受体对激动剂的亲和力。可乐定是一种高度特异性的α2-受体激动剂，经肠胃外给药时会产生短暂的高血压效应。我们在清醒的无肾Wistar大鼠中研究了等摩尔的生理盐水或甘露醇溶液对皮下注射剂量为10、100和1000微克/千克体重的可乐定所致高血压反应的影响。预先输注生理盐水使对两种较高剂量可乐定的高血压反应降低了65%和70%，并使剂量-反应曲线的斜率向下移动，但甘露醇没有这种作用。用α2-拮抗剂育亨宾预处理消除了生理盐水处理组、甘露醇处理组和对照组大鼠在可乐定诱导的升压反应上的差异。相反，用α1-拮抗剂哌唑嗪预处理后，与其他两组相比，生理盐水输注大鼠中可乐定的升压作用显著降低。因此，可乐定引起的升压反应的生理盐水诱导的减弱可被预先的α2-而非α1-阻断所消除，这表明钠干扰了突触后血管α2-肾上腺素能受体的刺激。这些发现表明，体内氯化钠负荷会减弱α2-肾上腺素能受体功能。基于此，我们认为钠过量导致血压升高的机制涉及α2-肾上腺素能受体的改变。
