Experimental effect and mechanism of N-acetylcysteine in preventing nitrate resistance
Chen Liang
Jiang Jinqi
Feng Hui
Zhang Ying
Abstract：Objective To observe the experimental effect of N-acetylcysteine (NAC) in preventing nitrate resistance and analyze relevant mechanism through establishing an animal model of isosorbide-5-mononitrate (ISMN) resistance. Methods Male adult New Zealand rabbits (n=32) with body mass=(2500±200) g were randomly divided into control group, routine group, drug-resistance group and NAC group (each n=8). The control group was not given any drugs, routine group was intragastrically given ISMN (25 mg/time) once a day, drug-resistance group, ISMN (25 mg/time) once every 12 h, and NAC group, ISMN (25 mg/time) and NAC (100 mg) once every 12 h. All rabbits were executed after 7 d and the abdominal aorta was collected and cut into segments (5 mm) for detecting vascular ring relaxation response, and levels of total sulfhydryl (T-SH, micro enzyme standard method), superoxide anion (O2-, chemical colorimetry), superoxide dismutase (SOD, xanthine oxidase method), malondialdehyde (MDA, thiobarbituric acid method), endothelin-1 (ET-1, double antibody sandwich method), and nitrite (NO2-, nitric acid reductase method). Results As the concentration of nitroglycerin (GTN) increased progressively, vascular ring relaxation amplitude of abdominal aorta increased in varying degrees in all groups. The vascular ring relaxation amplitude was lower in drug-resistance group than that in other 3 groups (all P<0.01), and the difference among control group, routine group and NAC group had no statistical difference (all P>0.05). When the concentration of GTN increased to 10-4mol/L, the vascular ring relaxation amplitude reached to (98.91±1.99) % in control group, (95.59±3.97) % in routine group, (93.18±6.36) % in NAC group, and only (63.62±6.03) % in drug-resistance group. The level of T-SH and SOD vitality showed a descending order in control group, NAC group, routine group and drug-resistance group (all P<0.05). While the levels of O2-, MDA, ET-1 and NO2- showed a descending order in drug-resistance group, routine group, NAC group and control group (all P<0.05). Conclusion Orally administrated NAC can prevent nitrate resistance and exert the effect of vascular dilation through increasing sulfhydryl level and inhibiting oxidative stress and generation of vasoconstrictive substance induced by ISMN.
Keywords：N-acetylcysteineNitrate resistanceIsosorbide-5-mononitrateSulfhydrylOxidative stressRabbits
Publication Date：2017-01-01
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：4( 1334-1337 )