Suliburska Joanna, Bogdanski Paweł, Jakubowski Hieronim
Department of Human Nutrition and Hygiene, Poznan University of Life Sciences, Poznan, Poland.
Department of Internal Medicine, Metabolic Disorders and Hypertension, University of Medical Sciences, Poznan, Poland.
Eur J Pharmacol. 2014 Sep 5;738:326-31. doi: 10.1016/j.ejphar.2014.06.003. Epub 2014 Jun 11.
Mineral homeostasis in hypertensive patients may be affected by hypotensive drugs. The aim of this study was to assess the influence of selected antihypertensive drugs on mineral homeostasis in a rat model of hypertension. Eight-week-old male spontaneously hypertensive rats (SHRs) were treated with perindopril, metoprolol, indapamide, amlodipine, or no drug for 45 days. In another experiment, the SHRs were treated with indapamide or amlodipine in the presence of zinc and copper gluconate supplement. Lipids, glucose, and insulin levels along with superoxide dismutase and catalase activities were assayed in serum. Iron, zinc, and copper concentrations in serum, erythrocytes, and tissues were determined using the flame atomic absorption spectrometry. Blood pressure was measured using a tail-cuff plethysmograph. Treatment with indapamide and amlodipine was found to significantly lower zinc levels in serum, erythrocytes, livers, and spleens of the SHRs, as well as copper levels in the kidneys, compared with the control no-drug group. A markedly higher concentration of glucose was found in the indapamide-treated rats. Supplementing the indapamide-treated SHRs with zinc and copper gluconate resulted in a significant decrease in both systolic and diastolic blood pressure, and also lowered serum glucose and triglyceride concentrations and HOMA (homeostasis model assessment-insulin resistance) values. The results show that indapamide and amlodipine disturb zinc and copper homeostasis in SHRs. Supplementation with zinc and copper restores mineral homeostasis in SHRs treated with indapamide and amlodipine, and also corrects metabolic imbalances while improving the antihypertensive efficiency of indapamide.
高血压患者的矿物质稳态可能会受到降压药物的影响。本研究的目的是评估所选抗高血压药物对高血压大鼠模型矿物质稳态的影响。8周龄雄性自发性高血压大鼠（SHRs）分别用培哚普利、美托洛尔、吲达帕胺、氨氯地平治疗45天，或不进行药物治疗。在另一项实验中，SHRs在补充葡萄糖酸锌和葡萄糖酸铜的情况下用吲达帕胺或氨氯地平治疗。测定血清中的脂质、葡萄糖和胰岛素水平以及超氧化物歧化酶和过氧化氢酶活性。使用火焰原子吸收光谱法测定血清、红细胞和组织中的铁、锌和铜浓度。使用尾套体积描记法测量血压。与未用药的对照组相比，发现用吲达帕胺和氨氯地平治疗可显著降低SHRs血清、红细胞、肝脏和脾脏中的锌水平，以及肾脏中的铜水平。在吲达帕胺治疗的大鼠中发现葡萄糖浓度明显更高。给用吲达帕胺治疗的SHRs补充葡萄糖酸锌和葡萄糖酸铜可导致收缩压和舒张压显著降低，还可降低血清葡萄糖和甘油三酯浓度以及HOMA（稳态模型评估-胰岛素抵抗）值。结果表明，吲达帕胺和氨氯地平扰乱了SHRs中的锌和铜稳态。补充锌和铜可恢复用吲达帕胺和氨氯地平治疗的SHRs中的矿物质稳态，还可纠正代谢失衡，同时提高吲达帕胺的降压效果。
