Animal Experiment On Chronotherapy Of Hypertension

Hypertension is one of the most common cardiovascular diseases in China, which brings about a prevalence rate of 11.6%. Lots of studies have confirmed that hypertension is an important risk factor for cardiovascular diseases. It is predicted that by the year 2020 the death rate caused by non-communicable diseases will reach to 79% of the total, in which hypertension contributes the most. It is therefore essential to control the levels of blood pressures (BP) among the public and to treat the hypertension patients promptly. The traditional way in anti-hypertension treatment is to give patients the same dose of medicine at equal intervals during a day. But usually it fails to keep the BP effectively under control over day and night. The development of chronotherapy makes it possible to reach this goal. In this paper, animal experiments on chronotherapy of hypertension were carried out to provide basic data for the future application of chronotherapy in human.(1) The establishment of hypertension model in rats: 16 SD rats were divided into two groups: (1) control group, 4 rats fed with normal feedstuff; (2) hypertension group, 12 rats fed with NG-nitro-L-arginine-methlester(L-NAME) for 6 weeks. Blood pressure of each rat of the two groups was measured continuously for 24 hours before and after the treatment. The data of BP were analyzed by a cosinor software to determine the circadian times corresponding to the parameters of peak, mean and vallecula.(2) Effect of circadian administration of enalapril on blood pressure, nitric oxide(NO) and endothelin(ET) of plasma in hypertension rats. Blood sample was taken by the caudal artery of each rat to measure the NO and ET in plasma. The hypertension rats were divided into 3 groups randomly according to the time point when enalapril (10 mg?kg-1 ? d-1) was given. The three time points are (1)3 hours before the peak time of the circadian rhythm; (2) 3 hours before the mean time of the circadian rhythm; (3) 3 hours before the trough time of the circadian rhythm. Enalapril was given to each rat daily at the dose of 10 mg?kg-1?day-1 for 2 weeks. The blood pressure of each rat was measured again for 24 hours to observe differences in the therapeutic effects.The result reveals that the BP of normal rats changes in a circadian pattern, with lower levels in the daytime and higher levels in the nighttime. The administration of L-NAME successfully induced a hypertension model in rats, which could be inhibited by enalapril. Compared with the hypertension rats at the above 3 time points, the BP after the enalapril decreased by 12.2%, 8.2% and 8.3%; the level of nitric oxide increased by 62.8%, 36.5% and 34.5%; and the plasma endothelin increased by 6.5%, 9.7% and 9.8%, respectively. It is clear that the treatment before the peak time of the BP circadian rhythm can result in a greatest effect on hypertension and the NO increase in a 24-hours day.