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Cardiovascular-Renal Mechanisms in Health and Disease

Nicotine: the link between cigarette smoking and the progression of renal injury?

¹Nephrology Section Veterans Affairs Medical Center, ²Renal Division, and the ³Vascular Biology Institute, Miller School of Medicine, University of Miami, Miami, Florida

Submitted 29 June 2006 ; accepted in final form 18 August 2006

Cigarette smoke (CS) is the most important source of preventable morbidity and mortality in the United States. Recent clinical studies have suggested that, in addition to being a major cardiovascular risk factor, CS promotes the progression of kidney disease. The mechanisms by which CS promotes the progression of chronic kidney disease have not been elucidated. Here we demonstrate for the first time that human mesangial cells (MCs) are endowed with the nicotinic ACh receptors (nAChRs) 4, 5, 7, 2, 3, and 4. Studies performed in other cell types have shown that these nAChRs are ionotropic receptors that function as agonist-regulated Ca²⁺ channels. Nicotine induced MC proliferation in a dose-dependent manner. At 10 ^–7 M, a concentration found in the plasma of active smokers, nicotine induced MC proliferation [control, 1,328 ± 50 vs. nicotine, 2,761 ± 90 counts/minute (cpm); P < 0.05] and increased the synthesis of fibronectin (50%), a critical matrix component involved in the progression of chronic kidney disease. We and others have shown that, in response to PKC activation, MC synthesize reactive oxygen species (ROS) via NADPH oxidase. In the current studies we demonstrate that PKC inhibition as well as diphenyleneiodonium and apocynin, two inhibitors of NADPH oxidase, prevented the effects of nicotine on MC proliferation and fibronectin production, hence establishing ROS as second messengers of the actions of nicotine. Furthermore, nicotine increased the production of ROS as assessed by 2',7'-dichlorofluorescein diacetate fluorescence [control, 184.4 ± 26 vs. nicotine, 281.5 ± 26 arbitrary fluorescence units (AFU); n = 5 experiments, P < 0.05]. These studies unveil previously unrecognized mechanisms that indict nicotine, a component of CS, as an agent that may accelerate and promote the progression of kidney disease.

glomerular mesangium; extracellular matrix; cell proliferation; reactive oxygen species

This article has been cited by other articles:

				S. R. Orth and S. I. Hallan Smoking: A Risk Factor for Progression of Chronic Kidney Disease and for Cardiovascular Morbidity and Mortality in Renal Patients Absence of Evidence or Evidence of Absence? Clin. J. Am. Soc. Nephrol., January 1, 2008; 3(1): 226 - 236. [Abstract] [Full Text] [PDF]