The Protective Effect of Captopril on Nicotine‐Induced Endothelial Dysfunction in Rat

Abstract

This study was designed to examine the in vivo and in vitro effects of captopril, an angiotensin-converting enzyme inhibitor, on nicotine-induced endothelial dysfunction in rats. Endothelial dysfunction was induced by exposing isolated rat mesenteric arteries to nicotine (0.01, 0.1, or 1 mM) for 24 hr using an organ culture system, or by treating rats with nicotine (2 mg/kg/day, intraperitoneally) for 4 weeks. The protective effects of captopril were tested by exposing isolated mesenteric arteries to captopril (0.01, 0.03, or 0.1 mM) π nicotine (0.1 mM) for 24 hr, or by treating rats with captopril (3 mg/kg/day, intravenously) π nicotine (2 mg/kg/day, intraperitoneally) for 4 weeks. Exposure of the isolated mesenteric arteries to nicotine induced a significant concentration -dependent inhibition of endothelium-dependent relaxation. Co-culture of segments of mesenteric artery with captopril (0.03 or 0.1 mM) attenuated the nicotine-induced impairment of vasorelaxation in a dose-dependent manner. Administration of nicotine to rats for 4 weeks significantly impaired endothelium-dependent relaxation compared with control rats. This impairment was accompanied by a reduction in nitrite/nitrate, nitric oxide (NO) synthase (NOS), and superoxide dismutase (SOD) activities in the serum and aorta. Chronic captopril treatment not only improved the impairment of endothelium-dependent relaxation, but also prevented the reduction of nitrite/nitrate contents and of NOS and SOD activities in the serum and aorta. However, there were no significant differences in serum angiotensin-converting enzyme activity among the three groups. These results indicate that captopril can be used to attenuate nicotine-induced endothelial dysfunction, an effect that may be related not only to antioxidation, but also to enhancing NO production by preventing the decrease in NOS.

Delayed preconditioning prevents ischemia/reperfusion-induced endothelial injury in rats: role of ROS and eNOS

“…At the end of the equilibration period, the contractile capacity of each ring was tested by exposure to a high-K þ Krebs' solution (obtained by equimolar replacement of NaCl by KCl in the Krebs' solution), and the ring was considered viable and used for experiments only if two reproducible high-K þ contractions were obtained. 20,22 Vascular Reactivity Studies Endothelium-dependent and -independent relaxations were assessed by measuring the dilatory responses of mesenteric arteries to cumulative concentrations of acetylcholine (ACh; 10 À 10 -10 À 5 mol/l) and sodium nitroprusside (SNP; 10 À 10 -10 À 5 mol/l), respectively. All experiments were performed in vessels pre-contracted with phenylephrine (PE; 10 mmol/l).…”

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