The protective effect of captopril on nicotine-induced endothelial dysfunction in rat.
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) + nicotine (0.1 mM) for 24 hr, or by treating rats with captopril (3 mg/kg/day, intravenously) + 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.
Luo
Hong-Li
HL
Department of Pharmacology, School of Medicine, Xi'an Jiaotong University, Xi'an 710061, China.
Zang
Wei-Jin
WJ
Lu
Jun
J
Yu
Xiao-Jiang
XJ
Lin
Yuan-Xi
YX
Cao
Yong-Xiao
YX
D000109:Acetylcholine / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D002216:Captopril / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology / Q000503:physiopathology; D005260:Female; D008297:Male; D009538:Nicotine / Q000633:toxicity*; D009638:Norepinephrine; D051381:Rats; D017207:Rats, Sprague-Dawley
D000806:Angiotensin-Converting Enzyme Inhibitors; D009538:Nicotine; D002216:Captopril; D000109:Acetylcholine; D009638:Norepinephrine