代谢物
循环系统
收缩性
哌唑嗪
血压
肠系膜动脉
药理学
内科学
内分泌学
血管阻力
化学
医学
动脉
受体
敌手
作者
Piotr Konopelski,Dawid Chabowski,Marta Aleksandrowicz,Ewa Koźniewska,Piotr Podsadni,A Szczepańska,Marcin Ufnal
出处
期刊:American Journal of Physiology-regulatory Integrative and Comparative Physiology
[American Physiological Society]
日期:2021-11-10
卷期号:321 (6): R969-R981
被引量:27
标识
DOI:10.1152/ajpregu.00142.2021
摘要
Recent evidence suggests that gut bacteria-derived metabolites interact with the cardiovascular system and alter blood pressure (BP) in mammals. Here, we evaluated the effect of indole-3-propionic acid (IPA), a gut bacteria-derived metabolite of tryptophan, on the circulatory system. Arterial BP, electrocardiographic, and echocardiographic (ECHO) parameters were recorded in male, anesthetized, 12-wk-old Wistar-Kyoto rats at baseline and after intravenous administration of either IPA or vehicle. In additional experiments, rats were pretreated with prazosin or pentolinium to evaluate the involvement of the autonomic nervous system in cardiovascular responses to IPA. IPA’s concentrations were measured using ultra-high performance liquid chromatography tandem mass spectrometry. The reactivity of endothelium-intact and -denuded mesenteric resistance arteries was tested. Cells’ viability and lactate dehydrogenase (LDH) cytotoxicity assays were performed on cultured cardiomyocytes. IPA increased BP with a concomitant bradycardic response but no significant change in QTc interval. The pretreatment with prazosin and pentolinium reduced the hypertensive response. ECHO showed increased contractility of the heart after the administration of IPA. Ex vivo, IPA constricted predilated and endothelium-denuded mesenteric resistance arteries and increased metabolic activity of cardiomyocytes. IPA increases BP via cardiac and vascular mechanisms in rats. Furthermore, IPA increases cardiac contractility and metabolic activity of cardiomyocytes. Our study suggests that IPA may act as a mediator between gut microbiota and the circulatory system.
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