Experimental study on the prevention of nitrate tolerance in rabbits with atherosclerosis by oral administration of sulfhydryl donor

Chen Liang; Jiang Jinqi; Feng Hui

doi:10.3969/j.issn.1674-4055.2017.12.10

Abstract：Objective To investigate the preventive value and mechanism of oral administration of sulfhydryl donor, N-acetylcysteine (NAC), on nitrate tolerance in rabbits with atherosclerosis (AS).Methods Abdominal aorta atherosclerosis models in 32 adult male New Zealand white rabbits were established by balloon denudation combined with high-fat diet. All rabbits were randomly divided into control group (AS group), nitrate group (ISMN group), nitrate tolerance group (NT group) and combination treatment group (NT+NAC group) (with 8 animals in each group). In AS group, no drugs were administrated. In ISMN group, isosorbide-5-mononitrate (ISMN) was administrated by gastric tube at the dose of 25 mg/ 24 h. In NT group, ISMN was administrated at the dose of 25 mg/12 h. And in NT+NAC group, combination drugs of ISMN (25 mg/12 h) and NAC (100 mg/12 h) were administrated. After 7 days of administration, abdominal aortas removed from all animals were cut into several 5 mm long segments for pathological observation, detection of vascular ring diastolic reaction, and measurement of the levels of total sulfhydryls (T-SH), superoxide anion (·O2-), superoxide dismutase (SOD), malondialdehyde (MDA) and endothelin-1 (ET-1).Results The abdominal aorta atherosclerosis models were successfully established in all rabbits. Vascular ring diastolic reaction in NT group was significantly weaker than that in other groups (P< 0.05). While in NT+NAC group, the vascular ring diastolic reaction was notably stronger than that in NT group (P<0.05) but was similar to that in AS group and ISMN group (P>0.05). The levels of ·O2-、MDA、ET-1 and NO2- in vascular tissues were respectively the highest in NT group, then in ISMN group, then in NT+NAC group, and the lowest in AS group. There was significant difference in each parameter among 4 groups (P<0.01) except in ·O2- level between AS group and NT+NAC group (P>0.05). On the contrary, the levels of SOD and T-SH were the highest in AS group, then in NT+NAC group, then in ISMN group, and the lowest in NT group. There were significant differences in both parameters between each group (P<0.05). Conclusion Oral administration of NAC can improve the effects of nitrates tolerance by supplementing sulfhydryl groups and inhibiting oxidative stress in rabbits with atherosclerosis.