Department of Physiology, Trakya University School of Medicine, Edirne, Turkey
Department of Pathology, Trakya University School of Medicine, Edirne, Turkey
Balkan Med J. 2019 Oct 28;36(6):337-346. doi: 10.4274/balkanmedj.galenos.2019.2019.5.113. Epub 2019 Sep 5.
The cause of about 95% of hypertension, an important public health problem, is unknown. Intensive studies are underway to understand the physiopathology of hypertension. Irisin, a newly discovered hormone, has been reported to dilate vascular smooth muscle and lower blood pressure acutely.
To investigate the effects of chronic irisin treatment on blood pressure and renal functions in a hypertension model established by nitric oxide synthase inhibition by treatment with Nω-nitro-L-arginine methyl ester hydrochloride.
Animal experimentation.
Male Sprague−Dawley rats were divided into four groups (n=8). Control and irisin groups received an intravenous saline injection, hypertension and hypertension + irisin (hypertension + irisin) groups received 1.5 mg/100 g Nω-nitro-L-arginine methyl ester hydrochloride. Nω-nitro-L-arginine methyl ester hydrochloride (150 mg/L) was added to the drinking water of rats in groups hypertension and hypertension + irisin for three weeks. In the second week of the experiment, irisin (50 nmol/day) was given to rats in groups irisin and hypertension + irisin, and saline was administered to rats in groups control and hypertension for two weeks through subcutaneously placed osmotic minipumps. Blood pressure was measured by the tail-cuff plethysmography method. On the twenty-first day of the experiment, 24-hour urine, blood, and both kidneys of the rats were collected.
The hypertension group had elevated systolic, diastolic, and mean arterial blood pressure values compared with the control group, with decreased glutathione levels in tissue and serum, but an increase in serum oxidized glutathione level (p<0.05). Histopathologically, increased tubular injury, cast formation, glomerular sclerosis, and peritubular fibrosis levels were observed (p<0.05). Irisin treatment did not cause any significant change in blood pressure, renal functions, and injury scores. However, renal nitric oxide levels significantly increased, and endothelial nitric oxide synthase immunoreactivity was determined to be reduced (p<0.05).
Treatment with chronic irisin at a physiological dose does not reduce blood pressure in an experimental model of hypertension. In different models of experimental hypertension, the effects of irisin administration at different doses and at different periods should be thoroughly investigated.
约 95%的高血压的病因尚未明确,高血压是一个重要的公共卫生问题。目前正在进行深入研究以了解高血压的病理生理学。新发现的激素鸢尾素可舒张血管平滑肌并降低血压。
研究慢性鸢尾素治疗对一氧化氮合酶抑制剂 Nω-硝基-L-精氨酸甲酯盐酸盐处理诱导的高血压模型大鼠血压和肾功能的影响。
动物实验。
雄性 Sprague-Dawley 大鼠随机分为 4 组(n=8)。对照组和鸢尾素组静脉注射生理盐水,高血压组和高血压+鸢尾素组(高血压+鸢尾素组)给予 1.5mg/100gNω-硝基-L-精氨酸甲酯盐酸盐。高血压组和高血压+鸢尾素组的大鼠饮用水中添加 150mg/LNω-硝基-L-精氨酸甲酯盐酸盐,共 3 周。实验第 2 周,给予鸢尾素组和高血压+鸢尾素组大鼠 50nmol/天的鸢尾素,对照组和高血压组大鼠通过皮下植入的渗透微型泵给予生理盐水,共 2 周。通过尾套测压法测量血压。实验第 21 天,收集大鼠 24 小时尿液、血液和双侧肾脏。
与对照组相比,高血压组大鼠的收缩压、舒张压和平均动脉压均升高,组织和血清中的谷胱甘肽水平降低,而血清氧化型谷胱甘肽水平升高(p<0.05)。组织病理学观察发现肾小管损伤、 casts 形成、肾小球硬化和肾小管周围纤维化程度增加(p<0.05)。鸢尾素治疗未引起血压、肾功能和损伤评分的显著变化。然而,肾一氧化氮水平显著升高,内皮型一氧化氮合酶免疫反应性降低(p<0.05)。
生理剂量的慢性鸢尾素治疗不能降低实验性高血压模型的血压。在不同的实验性高血压模型中,应彻底研究不同剂量和不同时期的鸢尾素给药的作用。