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慢性大麻素治疗可减少孤立性高血压大鼠心脏中乙酰胆碱诱导的冠状动脉收缩和左心室心肌细胞宽度。

Chronic cannabidiol treatment reduces the carbachol-induced coronary constriction and left ventricular cardiomyocyte width of the isolated hypertensive rat heart.

机构信息

Department of Experimental Physiology and Pathophysiology, Medical University of Białystok, Białystok, Poland.

Department of Experimental Physiology and Pathophysiology, Medical University of Białystok, Białystok, Poland.

出版信息

Toxicol Appl Pharmacol. 2021 Jan 15;411:115368. doi: 10.1016/j.taap.2020.115368. Epub 2020 Dec 16.

DOI:10.1016/j.taap.2020.115368
PMID:33338514
Abstract

Cannabidiol (CBD) is suggested to possess cardioprotective properties. We examined the influence of chronic (10 mg/kg once daily for 2 weeks) CBD administration on heart structure (e.g. cardiomyocyte width) and function (e.g. stimulatory and inhibitory responses induced by β-adrenoceptor (isoprenaline) and muscarinic receptor (carbachol) activation, respectively). Experiments were performed on hearts and/or left atria isolated from spontaneously (SHR) and deoxycorticosterone (DOCA-salt) hypertensive rats; Wistar-Kyoto (WKY) and sham-operated rats (SHAM) served as the respective normotensive controls. CBD diminished the width of cardiomyocytes in left ventricle and reduced the carbachol-induced vasoconstriction of coronary arteries both in DOCA-salt and SHR. However, it failed to affect left ventricular hypertrophy and even aggravated the impaired positive and negative lusitropic effects elicited by isoprenaline and carbachol, respectively. In normotensive hearts CBD led to untoward structural and functional effects, which occurred only in WKY or SHAM or, like the decrease in β-adrenoceptor density, in either control strain. In conclusion, due to its modest beneficial effect in hypertension and its adverse effects in normotensive hearts, caution should be taken when using CBD as a drug in therapy.

摘要

大麻二酚(CBD)被认为具有心脏保护作用。我们研究了慢性(每天 10 毫克/千克,持续 2 周)CBD 给药对心脏结构(例如,心肌细胞宽度)和功能(例如,β-肾上腺素能受体(异丙肾上腺素)和毒蕈碱受体(乙酰胆碱)激活分别诱导的刺激和抑制反应)的影响。在来自自发性高血压大鼠(SHR)和去氧皮质酮(DOCA-盐)高血压大鼠的心脏和/或左心房以及 Wistar-Kyoto(WKY)和假手术大鼠(SHAM)中进行了实验;分别作为各自的正常血压对照。CBD 减少了左心室心肌细胞的宽度,并降低了 DOCA-盐和 SHR 中乙酰胆碱诱导的冠状动脉收缩。然而,它未能影响左心室肥厚,甚至加重了异丙肾上腺素和乙酰胆碱分别引起的正性和负性舒张功能障碍。在正常血压的心脏中,CBD 导致了不良的结构和功能影响,这些影响仅发生在 WKY 或 SHAM 中,或者像β-肾上腺素能受体密度降低一样,仅发生在任一对照品系中。总之,由于 CBD 在高血压中的适度有益作用及其在正常血压心脏中的不良作用,在将 CBD 用作治疗药物时应谨慎。

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