Nicotine Impairs Smooth Muscle cAMP Signaling and Vascular Reactivity.

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.