Nicotine Modulates the Renin–Angiotensin System of Cultured Neurons and Glial Cells from Cardiovascular Brain Areas of Wistar Kyoto and Spontaneously Hypertensive Rats

Abstract

Considering the importance of the renin-angiotensin system (RAS) for the central control of blood pressure and that nicotine increases the probability of development of hypertension associated to genetic predisposition, our aims are (1) to determine RAS in cultured neurons and glia from the brainstem and hypothalamus of spontaneously hypertensive (SHR) and Wistar Kyoto (WKY) rats; (2) to analyze the possibility of nicotine to interact with brain RAS; and (3) to hypothesize any contribution of nicotine and RAS to the development of neurogenic hypertension. This study demonstrated physiological differences in RAS between cultured neuronal and glial cells from the brainstem and hypothalamus of SHR and WKY neonate rats. Our study also featured evidences of direct modulation of the RAS by nicotine in neurons and glia of brainstem and hypothalamus, which seems to be differential between the two rat strains. Such modulation gives us a clue about the mechanisms possibly involved in the genesis of neurogenic hypertension in vivo, for example, increase in angiotensin II type 1 receptor binding and decrease in angiotensin-converting enzyme 2. In conclusion, we demonstrated that neuronal and glial RAS from the brainstem and hypothalamus of SHR differ from WKY rats and nicotine differentially modulates the brain RAS in SHR and WKY.

Cigarette smoke exposure and inflammatory signaling increase the expression of the SARS-CoV-2 receptor ACE2 in the respiratory tract

“…Several contrasting findings exist in the literature on ACE2 and cigarette exposure 76–81 . In particular, it has been reported that nicotine and/or cigarette smoke has the potential to downregulate ACE2 expression in certain tissues or cell types 76–79 . In this manuscript, we focused our analysis on factors affecting ACE2 expression in the mammalian lungs and associated respiratory epithelia.…”

Nicotine and the renin-angiotensin system

“…The above results indicate that AT 1 R is involved in nicotine-evoked release of both dopamine and norepinephrine, and AT 1 R activation in striatum is counterbalanced by AT 2 R. Furthermore, nicotine exposure alters the expression and activity of the brain RAS. In primary cultures of neurons and glial cells isolated from brainstem and hypothalamus of 1-day-old rats, nicotine treatment resulted in increased expression of AT 1 R but decreased expression of ACE2, and these nicotine effects were greater in cells isolated from spontaneously hypertensive rats compared with Wistar-Kyoto rats (43,44). The above findings provide strong evidence that interaction between nicotine and the brain RAS may contribute to the sympatho-mimetic actions of nicotine as well as AT 1 R-mediated neurogenic hypertension (144).…”

Does COVID19 Infect the Brain? If So, Smokers Might Be at a Higher Risk

“…Smoking is a strong factor in predicting an individual's likelihood of developing and managing a viral infection and especially a respiratory infection (Razani-Boroujerdi et al, 2004;Eddleston et al, 2011). Here, we raise the question of nicotine-associated comorbidity to COVID19 in the context of the brain based on published evidence that the viral target receptor ACE2 is expressed in the brain and functionally interacts with nAChRs (Ferrari et al, 2007;Oakes et al, 2018). We consider if neural cells, such as epithelial cells, are more vulnerable to infection in https://doi.org/10.1124/molpharm.120.000014.…”