尼古丁会损害平滑肌环磷酸腺苷信号传导和血管反应性。
Nicotine Impairs Smooth Muscle cAMP Signaling and Vascular Reactivity.
作者信息
Singhrao Navid, Flores-Tamez Victor A, Moustafa Yumna A, Reddy Gopireddy R, Burns Abby E, Pinkerton Kent E, Chen Chao-Yin, Navedo Manuel F, Nieves-Cintrón Madeline
机构信息
Department of Pharmacology, University of California, Davis, California, USA.
Center for Health and the Environment, University of California, Davis, California, USA.
出版信息
Microcirculation. 2024 Aug;31(6):e12871. doi: 10.1111/micc.12871. Epub 2024 May 28.
OBJECTIVE
This study aimed to determine nicotine's impact on receptor-mediated cyclic adenosine monophosphate (cAMP) synthesis in vascular smooth muscle (VSM). We hypothesize that nicotine impairs β adrenergic-mediated cAMP signaling in VSM, leading to altered vascular reactivity.
METHODS
The effects of nicotine on cAMP signaling and vascular function were systematically tested in aortic VSM cells and acutely isolated aortas from mice expressing the cAMP sensor Epac (Camper), specifically in VSM (e.g., Camper).
RESULTS
Isoproterenol (ISO)-induced β-adrenergic production of cAMP in VSM was significantly reduced in cells from second-hand smoke (SHS)-exposed mice and cultured wild-type VSM treated with nicotine. The decrease in cAMP synthesis caused by nicotine was verified in freshly isolated arteries from a mouse that had cAMP sensor expression in VSM (e.g., Camper mouse). Functionally, the changes in cAMP signaling in response to nicotine hindered ISO-induced vasodilation, but this was reversed by immediate PDE3 inhibition.
CONCLUSIONS
These results imply that nicotine alters VSM β adrenergic-mediated cAMP signaling and vasodilation, which may contribute to the dysregulation of vascular reactivity and the development of vascular complications for nicotine-containing product users.
目的
本研究旨在确定尼古丁对血管平滑肌（VSM）中受体介导的环磷酸腺苷（cAMP）合成的影响。我们假设尼古丁会损害VSM中β肾上腺素能介导的cAMP信号传导，从而导致血管反应性改变。
方法
在表达cAMP传感器Epac（Camper）的小鼠的主动脉VSM细胞和急性分离的主动脉中，系统地测试了尼古丁对cAMP信号传导和血管功能的影响，特别是在VSM中（例如Camper）。
结果
在二手烟（SHS）暴露小鼠的细胞和用尼古丁处理的培养野生型VSM中，异丙肾上腺素（ISO）诱导的VSM中cAMP的β肾上腺素能产生显著降低。尼古丁引起的cAMP合成减少在VSM中具有cAMP传感器表达的小鼠（例如Camper小鼠）的新鲜分离动脉中得到证实。在功能上，尼古丁引起的cAMP信号变化阻碍了ISO诱导的血管舒张，但通过立即抑制PDE3可逆转这一现象。
结论
这些结果表明，尼古丁会改变VSM中β肾上腺素能介导的cAMP信号传导和血管舒张，这可能导致含尼古丁产品使用者的血管反应性失调和血管并发症的发生。
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