Honig A, Wedler B, Zingler C, Ledderhos C, Schmidt M
Biomed Biochim Acta. 1985;44(11-12):1659-72.
The reactions of the mean systemic arterial blood pressure, arterial acid-base balance kidney function (clearance-technique), and plasma aldosterone concentration (radio-immunoassay) elicited by stimulation of the peripheral arterial chemoreceptors with almitrine bismesylate were determined in chloralosed, non-vagotomized, spontaneously breathing cats in moderate mannitol-saline diuresis. The left renal nerves were cut; urine was collected separately from both the innervated and denervated kidneys. Intravenous injection of 0.2 mg/kg of the drug caused the expected long-lasting increase of the pO2 and pH and a decrease of pCO2 in the arterial blood, whereas the mean systemic arterial blood pressure slightly rose by an average of 2-4 mm Hg in the first hour of chemoreceptor stimulation but afterwards considerably decreased below the pre-injection values. The renal responses were characterized by a moderate vasoconstriction particularly in the innervated kidneys and a pronounced increase of sodium and urine excretion especially in the denervated kidneys. The inhibition of renal tubular sodium reabsorption underlying these natriuretic and diuretic reactions was fully demonstrable even at the end of the experiments, i. e. 4 h after the administration of the agent. Plasma aldosterone increased with the time of the experiments but did not show any clear relationships to the activity of the arterial chemoreceptors. The results show that the intravenous injection of almitrine bismesylate is connected with a renal response pattern which is typical for an excitation of the peripheral arterial chemoreceptors, i. e. moderate vasoconstriction (efferently mediated by the renal nerves) and an inhibition of renal tubular sodium reabsorption (efferently mediated by hormonal mechanisms). Furthermore, the data suggest that, on the one hand, under certain conditions these reactions of the kidney function could play the role of undesirable side effects but, on the other hand, the inhibition of renal tubular sodium reabsorption caused by almitrine bismesylate might possibly be used to treat diseases that are connected with a reduced ability of the kidneys to sufficiently excrete sodium.
在水合氯醛麻醉、未切断迷走神经、自主呼吸且处于中度甘露醇 - 盐水利尿状态的猫身上,测定了用二甲磺酸阿米三嗪刺激外周动脉化学感受器所引发的平均体循环动脉血压、动脉酸碱平衡、肾功能(清除技术)以及血浆醛固酮浓度(放射免疫测定)的反应。切断左侧肾神经;分别从有神经支配和去神经支配的肾脏收集尿液。静脉注射0.2mg/kg的该药物导致动脉血中pO2和pH值预期的持久升高以及pCO2降低,而在化学感受器刺激的第一个小时内,平均体循环动脉血压平均略有升高2 - 4mmHg,但随后大幅下降至注射前值以下。肾脏反应的特征是中度血管收缩,特别是在有神经支配的肾脏中,以及钠和尿液排泄显著增加,特别是在去神经支配的肾脏中。即使在实验结束时,即给药4小时后,这些利钠和利尿反应所基于的肾小管钠重吸收抑制仍完全可证实。血浆醛固酮随实验时间增加,但与动脉化学感受器的活性没有任何明显关系。结果表明,静脉注射二甲磺酸阿米三嗪与外周动脉化学感受器兴奋所特有的肾脏反应模式相关,即中度血管收缩(由肾神经传出介导)和肾小管钠重吸收抑制(由激素机制传出介导)。此外,数据表明,一方面,在某些情况下,这些肾功能反应可能起不良副作用的作用,但另一方面,二甲磺酸阿米三嗪引起的肾小管钠重吸收抑制可能可用于治疗与肾脏充分排泄钠能力降低相关的疾病。