Bryniarski Paweł, Nazimek Katarzyna, Marcinkiewicz Janusz
Department of Immunology, Jagiellonian University Medical College, 18 Czysta Street, 31-121 Krakow, Poland.
Int J Mol Sci. 2021 Dec 22;23(1):74. doi: 10.3390/ijms23010074.
Hypertension is a chronic disease associated with chronic inflammation involving activated macrophages. Antihypertensive drugs (for example, angiotensin-converting enzyme inhibitors-ACEIs) used in the treatment of hypertension have immunomodulatory properties. On the other hand, the immunological effect of diuretics and combined drugs (diuretics + ACEI) is unclear. Therefore, we examined the influence of diuretics and combination drugs (ACEI + diuretic) on cellular response (contact hypersensitivity), production of reactive oxygen intermediates (ROIs), and nitric oxide (NO), and the secretion of interleukin-12 (IL-12). CBA mice were administered i.p. captopril (5 mg/kg) with or without hydrochlorothiazide (10 mg/kg) or furosemide (5 mg/kg) for 8 days. On the third day, the mice were administered i.p. mineral oil, and macrophages were collected 5 days later. In the presented results, we show that diuretics administered alone or with captopril increase the generation of ROIs and reduce the formation of NO by macrophages. Moreover, tested drugs inhibit the secretion of IL-12. Diuretics and combined drugs reduce the activity of contact hypersensitivity (both activation and induction phases). Our research shows that the tested drugs modulate the cellular response by influencing the function of macrophages, which is important in assessing the safety of antihypertensive therapy.
高血压是一种与涉及活化巨噬细胞的慢性炎症相关的慢性疾病。用于治疗高血压的抗高血压药物（例如，血管紧张素转换酶抑制剂 - ACEIs）具有免疫调节特性。另一方面，利尿剂和复方药物（利尿剂 + ACEI）的免疫作用尚不清楚。因此，我们研究了利尿剂和复方药物（ACEI + 利尿剂）对细胞反应（接触性超敏反应）、活性氧中间体（ROIs）和一氧化氮（NO）的产生以及白细胞介素 - 12（IL - 12）分泌的影响。对CBA小鼠腹腔注射卡托普利（5毫克/千克），同时或不同时腹腔注射氢氯噻嗪（10毫克/千克）或呋塞米（5毫克/千克），持续8天。在第三天，给小鼠腹腔注射矿物油，5天后收集巨噬细胞。在呈现的结果中，我们表明单独使用或与卡托普利联合使用的利尿剂会增加ROIs的产生，并减少巨噬细胞产生NO。此外，受试药物抑制IL - 12的分泌。利尿剂和复方药物会降低接触性超敏反应的活性（激活期和诱导期）。我们的研究表明，受试药物通过影响巨噬细胞的功能来调节细胞反应，这对于评估抗高血压治疗的安全性很重要。
