Department of Pharmacology and Biochemistry, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa, Egypt.
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt; Department of Pharmacology and Toxicology, Faculty of Medicine, Kuwait University, Kuwait.
Eur J Pharmacol. 2021 May 5;898:173996. doi: 10.1016/j.ejphar.2021.173996. Epub 2021 Mar 5.
Angiogenesis accelerates tissue regeneration in a variety of ischemic conditions including myocardial infarction (MI). Here we tested the hypothesis that angiogenesis induced by α7-nicotinic acetylcholine receptors (α7-nAChRs) mitigates histopathological, electrocardiographic, and molecular consequences of MI in rats. These profiles were evaluated in the isoprenaline (85 mg/kg/day i. p. For 2 days) MI rat model treated with or without nicotine or PHA-543613 (PHA, selective α7-nAChR agonist). Isoprenaline-insulted rats showed (i) ECG signs of MI such as significant ST-segment elevations and prolonged QT-intervals, (ii) deteriorated left ventricular histopathological scoring and elevated inflammatory cell infiltration, (iii) reduced immunohistochemical expression of cardiac CD34, a surrogate marker of capillary density, (iv) decreased cardiac expression of iNOS and α7-nAChRs, and (v) adaptive increases in cardiac HO-1 expression and plasma angiogenic markers such as vascular endothelial growth factor (VEGF) and nitric oxide (NO). These effects of isoprenaline, except cardiac iNOS and α7-nAChRs downregulation, were ameliorated in rats treated with a low dose (20 μg/kg/day s. c. For 16 days) of nicotine or PHA. We also show that concurrent α7-nAChR blockade by methyllycaconitine (MLA, 40 μg/kg/day, for 16 days) reversed the ECG, histopathological, and capillary density effects of nicotine, thereby reinforcing the advantageous cardioprotective and anti-ischemic roles of α7-nAChRs in this setting. The observed results showed promising effects on isoprenaline induced myocardial damage. In conclusion, the activation of α7-nAChRs by doses of nicotine or PHA in the microgram scale promotes neovascularization and offers a promising therapeutic strategy for MI. CATEGORY: Cardiovascular Pharmacology.
血管生成加速了多种缺血情况（包括心肌梗死）中的组织再生。在这里，我们测试了一个假设，即α7-烟碱型乙酰胆碱受体（α7-nAChRs）诱导的血管生成可以减轻异丙肾上腺素（85mg/kg/天，腹腔注射，连续 2 天）诱导的心肌梗死大鼠模型的组织病理学、心电图和分子后果。在异丙肾上腺素损伤的大鼠模型中，我们观察到（i）心电图出现心肌梗死的迹象，如 ST 段显著抬高和 QT 间期延长，（ii）左心室组织病理学评分恶化，炎症细胞浸润增加，（iii）心脏 CD34 的免疫组织化学表达减少，CD34 是毛细血管密度的替代标志物，（iv）心脏 iNOS 和 α7-nAChRs 的表达减少，（v）心脏 HO-1 表达和血管生成标志物（如血管内皮生长因子（VEGF）和一氧化氮（NO））的血浆水平适应性增加。除心脏 iNOS 和 α7-nAChRs 下调外，异丙肾上腺素的这些作用在接受低剂量（20μg/kg/天，皮下注射，连续 16 天）尼古丁或 PHA 治疗的大鼠中得到改善。我们还表明，同时用甲基六氢吡啶（MLA，40μg/kg/天，连续 16 天）阻断α7-nAChR 可逆转尼古丁的心电图、组织病理学和毛细血管密度作用，从而加强了在这种情况下α7-nAChRs 的有利心脏保护和抗缺血作用。观察到的结果对异丙肾上腺素诱导的心肌损伤有积极的影响。总之，尼古丁或 PHA 在微克范围内激活α7-nAChRs 可促进血管新生，为心肌梗死提供了一种有前景的治疗策略。分类：心血管药理学。
