Nicotine Impairs Smooth Muscle cAMP Signaling and Vascular Reactivity

IF 1.9 4区医学 Q3 HEMATOLOGY

Microcirculation Pub Date : 2024-05-28 DOI:10.1111/micc.12871

Navid Singhrao, Victor A. Flores-Tamez, Yumna A. Moustafa, Gopireddy R. Reddy, Abby E. Burns, Kent E. Pinkerton, Chao-Yin Chen, Manuel F. Navedo, Madeline Nieves-Cintrón

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Abstract

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 ^TEpac^VV (Camper), specifically in VSM (e.g., Camper_SM).

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_SM 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.

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尼古丁会损害平滑肌 cAMP 信号和血管反应性

研究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血管平滑肌中β肾上腺素能介导的cAMP信号转导，从而导致血管反应性改变：方法：在表达 cAMP 传感器 TEpacVV（Camper）的小鼠主动脉 VSM 细胞和急性分离的主动脉（如 CamperSM）中系统测试了尼古丁对 cAMP 信号传导和血管功能的影响：结果：在暴露于二手烟（SHS）的小鼠细胞和用尼古丁处理的野生型 VSM 培养细胞中，异丙肾上腺素（ISO）诱导的 VSM 中 β 肾上腺素能产生的 cAMP 显著减少。尼古丁导致的 cAMP 合成减少在 VSM 中表达了 cAMP 传感器的小鼠（如 CamperSM 小鼠）新鲜分离的动脉中得到了验证。从功能上讲，尼古丁导致的 cAMP 信号变化阻碍了 ISO 诱导的血管扩张，但立即抑制 PDE3 可逆转这种情况：这些结果表明，尼古丁会改变 VSM β 肾上腺素能介导的 cAMP 信号转导和血管舒张，这可能会导致血管反应性失调，并导致含尼古丁产品使用者出现血管并发症。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Microcirculation 医学-外周血管病

CiteScore

5.00

自引率

4.20%

发文量

审稿时长

6-12 weeks

期刊介绍： The journal features original contributions that are the result of investigations contributing significant new information relating to the vascular and lymphatic microcirculation addressed at the intact animal, organ, cellular, or molecular level. Papers describe applications of the methods of physiology, biophysics, bioengineering, genetics, cell biology, biochemistry, and molecular biology to problems in microcirculation. Microcirculation also publishes state-of-the-art reviews that address frontier areas or new advances in technology in the fields of microcirculatory disease and function. Specific areas of interest include: Angiogenesis, growth and remodeling; Transport and exchange of gasses and solutes; Rheology and biorheology; Endothelial cell biology and metabolism; Interactions between endothelium, smooth muscle, parenchymal cells, leukocytes and platelets; Regulation of vasomotor tone; and Microvascular structures, imaging and morphometry. Papers also describe innovations in experimental techniques and instrumentation for studying all aspects of microcirculatory structure and function.