Nicotine and the renin-angiotensin system

Am J Physiol Regul Integr Comp Physiol. 2018 Nov 1;315(5):R895-R906. doi: 10.1152/ajpregu.00099.2018. Epub 2018 Aug 8.


Cigarette smoking is the single most important risk factor for the development of cardiovascular and pulmonary diseases (CVPD). Although cigarette smoking has been in constant decline since the 1950s, the introduction of e-cigarettes or electronic nicotine delivery systems 10 yr ago has attracted former smokers as well as a new generation of consumers. Nicotine is a highly addictive substance, and it is currently unclear whether e-cigarettes are "safer" than regular cigarettes or whether they have the potential to reverse the health benefits, notably on the cardiopulmonary system, acquired with the decline of tobacco smoking. Of great concern, nicotine inhalation devices are becoming popular among young adults and youths, emphasizing the need for awareness and further study of the potential cardiopulmonary risks of nicotine and associated products. This review focuses on the interaction between nicotine and the renin-angiotensin system (RAS), one of the most important regulatory systems on autonomic, cardiovascular, and pulmonary functions in both health and disease. The literature presented in this review strongly suggests that nicotine alters the homeostasis of the RAS by upregulating the detrimental angiotensin-converting enzyme (ACE)/angiotensin (ANG)-II/ANG II type 1 receptor axis and downregulating the compensatory ACE2/ANG-(1-7)/Mas receptor axis, contributing to the development of CVPD.

Keywords: brain; heart; lung; nicotine; renin-angiotensin system.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Humans
  • Nicotine / pharmacology*
  • Peptidyl-Dipeptidase A / drug effects*
  • Peptidyl-Dipeptidase A / metabolism
  • Receptor, Angiotensin, Type 1 / drug effects
  • Receptor, Angiotensin, Type 1 / metabolism
  • Renin-Angiotensin System / physiology*
  • Smoking*
  • Tobacco Products


  • Receptor, Angiotensin, Type 1
  • Nicotine
  • Peptidyl-Dipeptidase A