Department of Cardiology, Aviation General Hospital, Beijing, 10016, China.
Department of Emergency, Anzhen Hospital, Capital Medical University, Beijing, 100029, China.
BMC Cardiovasc Disord. 2020 Feb 27;20(1):99. doi: 10.1186/s12872-020-01353-z.
Few studies examined the effect of long-acting nitrates on renal function in chronic heart failure (CHF). Thus, we aimed to investigate the effect of long-acting nitrate on the expression of adrenoceptors (AR) and angiotensin II receptor (ATR) subtypes of the renal cortex, in rats with myocardial infarction-induced CHF.
Rats were randomly divided into the following groups: control, sham-operated, CHF, low- and high-dose nitrate, positive drug control (olmesartan), and high-dose of long-acting nitrate + olmesartan. Ultrasound echocardiography markers were compared, and the levels of AR subtypes, ATR, and ATR were measured using reverse transcription-polymerase chain reaction and western blot analysis. Histopathology of the kidney was determined on hematoxylin and eosin-stained sections.
CHF significantly increased plasma renin activity (PRA) and angiotensin II levels, upregulated ATR expression and downregulated α-, β-, β-AR, and ATR expression compared to the sham control. High-dose nitrate or olmesartan alone, and especially in combination, decreased the levels of PRA and angiotensin II and downregulated the CHF-induced expression of ATR, α-, β-, and β-AR, and ATR. CHF resulted in significant impairment of the renal tissue, including inflammatory cells infiltration to the tubular interstitium and surrounding the renal glomerulus, and tubular necrosis, which was alleviated in all treatment groups to different degrees.
Long-acting nitrates could reverse CHF-induced changes in AR and ATR subtypes in the kidney, and improve cardiac function to protect renal function. Compared with monotherapy, the combination of nitrates and olmesartan shows more significant benefits in regulating AR and ATR subtypes.
很少有研究探讨长效硝酸酯类药物对慢性心力衰竭（CHF）患者肾功能的影响。因此，我们旨在研究长效硝酸酯类药物对心肌梗死后 CHF 大鼠肾皮质肾上腺素能受体（AR）和血管紧张素 II 受体（ATR）亚型表达的影响。
将大鼠随机分为以下几组：对照组、假手术组、CHF 组、低剂量和高剂量硝酸盐组、阳性药物对照组（奥美沙坦）和高剂量长效硝酸盐+奥美沙坦组。比较超声心动图标志物，采用逆转录聚合酶链反应和 Western blot 分析检测 AR 亚型、ATR 和 ATR 的水平。对肾组织进行苏木精和伊红染色，观察组织病理学变化。
与假手术对照组相比，CHF 组显著增加了血浆肾素活性（PRA）和血管紧张素 II 水平，上调了 ATR 表达，下调了 α-、β-、β-AR 和 ATR 表达。单独使用高剂量硝酸盐或奥美沙坦，特别是两者联合使用，可降低 PRA 和血管紧张素 II 水平，并下调 CHF 诱导的 ATR、α-、β-和β-AR 及 ATR 表达。CHF 导致肾组织明显损伤，包括炎性细胞浸润肾小管间质和肾小球周围，以及肾小管坏死，所有治疗组均在不同程度上减轻了这种损伤。
长效硝酸酯类药物可逆转 CHF 引起的肾脏 AR 和 ATR 亚型变化，改善心功能，保护肾功能。与单药治疗相比，硝酸盐和奥美沙坦联合治疗在调节 AR 和 ATR 亚型方面具有更显著的益处。
