E-Cigarette Smoke Exposure Elevates Renal MR Expression and Induces BP Elevation

E-cigarette use increases the risk of blood pressure (BP) elevation in users, though the underlying mechanisms remain unclear. The mineralocorticoid receptor (MR) is known to play an important role in the regulation of renal electrolyte balance and BP, and is protected by 11β-HSD2 (11β-hydroxysteroid dehydrogenase type 2). However, little is known about the effects of renal MR on e-cigarette-induced BP elevation.

C57BL/6J male mice were exposed to aerosolized PBS, e-cigarettes without nicotine, and e-cigarettes with 2.4% nicotine, with concurrent exposure to either a vehicle or the MR antagonist eplerenone.

Inhalation of e-cigarettes with nicotine markedly induced renal MR abundance and increased mean arterial BP in response to elevated plasma nicotine levels in C57BL/6J mice. Induction of MR by e-cigarettes was correlated with a reduction in 11β-HSD2 and activation of pSer⁹GSK3β (glycogen synthase kinase-3β phosphorylation) within the kidneys. In contrast, e-cigarettes increased the urinary ratio of corticosterone to 11-dehydrocorticosterone, reduced urinary sodium content, and elevated renal epithelial sodium channel expression. However, inhaling e-cigarettes without nicotine did not affect these metabolic parameters. Treatment with eplerenone normalized BP, reversed urinary metabolic profiles, and reduced epithelial sodium channel by inhibiting renal pSer⁹GSK3β in nicotine e-cigarette-exposed mice. In mouse renal Cortical Collecting Duct (CCD) M1 cells, aerosol nicotine from e-cigarettes increased MR while decreasing 11β-HSD2, and these effects are likely via activation of pSer⁹GSK3β through a nicotinic receptor-mediated mechanism.

Our findings highlight the potential renal health damage from e-cigarettes and suggest that aerosol nicotine-mediated induction of MR action in the kidneys may contribute to electronic smoking-induced BP elevation.