Journal of Pharmacological Sciences
Online ISSN : 1347-8648
Print ISSN : 1347-8613
ISSN-L : 1347-8613
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Chronic Administration of Nicotine-Free Cigarette Smoke Extract Impaired Endothelium-Dependent Vascular Relaxation in Rats via Increased Vascular Oxidative Stress
Takashi ShimosatoAyman GeddawyMasashi TawaTakeshi ImamuraTomio Okamura
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2012 Volume 118 Issue 2 Pages 206-214

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Abstract
Cigarette smoking has been implicated in the initiation and progression of cardiovascular disorders and atherosclerosis. Here, we examined the effects of nicotine-free cigarette smoke extract (CSE) on the regulation of cardiovascular function. Rats were subcutaneously administered PBS or nicotine-free CSE at 0.05 to 1.5 mL/day per rat for 4 weeks. Blood pressure, cardiac function, and vascular responsiveness were measured at 4 weeks after administration. Furthermore, acute effects of nicotine-free CSE were also studied in the aorta isolated from normal rats. Blood pressure and left ventricular systolic pressure (LVSP) were significantly increased in the nicotine-free CSE–administered rats, but heart rate, dP/dtmax, and dP/dtmin were not affected. Endothelium-dependent relaxation by acetylcholine (ACh) in the nicotine-free CSE–treated rats was significantly attenuated compared to PBS-treated rats, but endothelium-independent relaxation by sodium nitroprusside (SNP) did not differ. Pretreatment with superoxide dismutase restored the attenuated ACh-induced relaxation. Contractions by phenylephrine, angiotensin II, and KCl did not differ between two groups. In vitro acute nicotine-free CSE treatment did not alter the response to ACh or SNP. These results suggest that chronic nicotine-free CSE administration impairs endothelial function by increased production of superoxide derived from the vascular wall components other than smooth muscles and induces slight hypertension accompanied with LVSP elevation.
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© The Japanese Pharmacological Society 2012
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