Chronic Administration of Nicotine-Free Cigarette Smoke Extract Impaired Endothelium-Dependent Vascular Relaxation in Rats via Increased Vascular Oxidative Stress

Journal of Pharmacological Sciences

Ayman Geddawy¹  Tomio Okamura¹  Masashi Tawa¹  Takashi Shimosato¹  Takeshi Imamura¹ 

[1] Department of Pharmacology, Shiga University of Medical Science, Japan

关键词: chronic administration;    nicotine-free cigarette smoke extract;    endothelial function;    superoxide;   

DOI  :  10.1254/jphs.11187FP

学科分类：药学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(39)Cited-By(6)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.

【 授权许可】

Unknown