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Objective: Blood pressure is the pressure of the blood on the side of the unit area of ??the vessel wall intravascular flow, is the premise of the tissues and organs of blood perfusion to meet the metabolic needs of the body, and thus to maintain the body's life. It is subject to the heart stroke output, heart rate, peripheral resistance, a variety of factors, and with the changes in these factors constant fluctuations. In most cases, this fluctuation is not random, but exhibits a certain rhythm. Its rhythm cycle of about 24 hours, it is known as the circadian rhythm (diurnal rhythm) or circadian rhythm (circadian rhythm). Circadian fluctuations of blood pressure can be divided into four types: (1) dipper (dippers): nighttime blood pressure than day decline of 10% to 20%; ② The non-dipper (non-dippers): 0% nocturnal blood pressure fall to 10%; ③ The ultra-dipper or deep dipper (over-dippers or extreme-dippers): night dropped gt; 20%; ④ anti-dipper (reverse-dippers): nighttime blood pressure levels higher than during the day. Is generally believed that the day and high night low-dipper blood pressure for humans is relatively healthy. In hypertensive patients, the elderly, and even part of the healthy population, the circadian rhythm of blood pressure characteristics may change. As we all know, with the rise of blood pressure levels, target organ damage and cardiovascular and cerebrovascular event rate was significantly higher. But in the case of blood pressure similar to the overall level of risk of target organ damage and cardiovascular and cerebrovascular events occurred, when the weakening or disappearance of the circadian rhythm also increased significantly. Therefore, to maintain blood pressure, antihypertensive treatment, while dipper distribution has important clinical significance of reducing target organ damage, reduce the incidence of cardiovascular and cerebrovascular events. Although active and effective non-drug treatment (such as adjusting diet, lose weight, improve on the way) is the cornerstone of antihypertensive therapy, blood pressure control is still mainly dependent on antihypertensive drugs. Different the buck mechanisms and different medication time may affect the regulation of the drugs on blood pressure and its circadian rhythm. To fully understand the impact of different antihypertensive drugs with different medication time on the circadian rhythm of blood pressure, help correct abnormal blood pressure rhythm, maintaining its normal rhythm. Although the formation mechanism of the circadian rhythm is not entirely clear, but some scholars at home and abroad have confirmed that endothelin -1 (ET-1), nitric oxide (NO), endothelium-derived nitric oxide synthase (NOS) plasma concentrations of vasoactive substances or activity typical circadian rhythm, and in the regulation of blood pressure and its circadian rhythm plays a very important role. Different antihypertensive drugs with different medication time characteristics of endothelium-derived vasoactive substances Chronobiology and circadian blood pressure remains to be discussed. This study to rats as experimental subjects research designed to explore the characteristics of circadian rhythm of blood pressure and the endothelial vasoactive substances and hydrogen chlorothiazide with different medication time their activity levels and circadian rhythm. Method: clean healthy male SD rats were 128, 10 weeks old, weighing 250-300 g, were randomly divided into four groups: the drugged group (MT), 19:00 drench group (NT) as early as 07:00 As early as the control group (MC) and late control group (NC). Irrigation drug group given the hydrochlorothiazide 10mg/Kg / day, the control group, respectively, as early as 07:00 or 19:00 irrigation volume of placebo (distilled water). Each group of 32. Each group was divided into 4 groups, each group of eight each. Feeding after 4 weeks of dosing according to the above programs, respectively, within 24 hours on the same day at different times the point (02:00,08:00,14:00,20:00) with rat tail manometry, measured the rats blood pressure and killed MT group, a small group of NT group, MC group, NC group rats. Were used to detect the expression levels of NO, eNOS, ET-1 concentration or activity and myocardial tissue eNOSmRNA rat blood and myocardial tissue. Application cosine fitting analysis of the biological characteristics of each of the four groups of experimental animal serum and myocardial tissue indexes content or activity time, zero-amplitude test (zeroamplitude test) the evaluation indexes circadian rhythms are really present, compare the application of analysis of variance The significant difference between the mean, p lt; 0.05 considered statistically significant difference. Results: Analysis of variance showed that dose group (MT group and NT group) in the blood and myocardial tissue content of NO, eNOS activity, myocardial eNOSmRNA expression of average water average significantly higher than that in the control group (MC group and NC group) (P lt; 0.05) by ET-1 content significantly lower than the control group (P lt; 0.05), while in the MT group and NT group and the MC group and NC group above vascular active substance level without significantly with differences (P gt; 0.05) . Step hydrochlorothiazide can affect the normal rats, ET-1, NO, of eNOS, eNOSmRNA expression. Two pairs of the four groups of rats blood and myocardial ET-1, NO, eNOS myocardial eNOSmRNA results are applied method of least squares fitting cosine draw each fitting curve and eigenvalues. The zero amplitude test shows, the measured values ??in the blood and myocardial showed a typical circadian rhythm. MC group, the NC group, MT group, NT group blood myocardial tissue ET-1 peak time located 22:28,22:27,21:02,21:33 01:49,02:13,00:34 01:12, NO peak time located 10:40,10:26,08:53,09:27 14:33,15:03,13:10,13:33, of eNOS peak time are located at 7:51, the highest level the 08:40,05:56,06:40 with 12:37,12:26,09:45,10:23, the myocardial eNOSmRNA expression in 11:35,11:54,08:37,08:58 or so. Compared with the control group, NO content, eNOS activity, eNOSmRNA expression levels larger the peak amplitude of the administration group, the peak amplitude of the ET-1 content smaller advance were above indicators peak time. Above indicators peak, amplitude, peak time, there was no significant difference in the MT group and NT group and the MC group and NC group. Step hydrochlorothiazide can affect the normal rats, the peak of each of the above indicators and amplitude, and its peak time in advance, and has nothing to do with the medication time. 3 analysis of variance showed that the the administration group average blood pressure was significantly lower than the control group (P lt; 0.05), while in the MT group and NT group and the MC group and NC group no significant difference (P gt; 0.05) indicate different medication time had no significant effect on the antihypertensive effect of hydrochlorothiazide. MC, NC, MT, NT 4 pairs of four groups of rats on blood pressure results are applied method of least squares cosine fit shows zero amplitude inspection, four groups of rats showed typical circadian rhythm of blood pressure, and its peak in 20:40 The, 21:10,19:28,20:05. Compared with the control group, the peak and the amplitude of the administration group significantly reduced peak times some advance above indicators were no significant differences in the MC group and NC group and the MT group and NT group. Conclusion: The four groups of rats blood pressure and blood, and (or) in cardiac tissue NO, eNOS, ET-1, water eNOSmRNA average showed typical circadian rhythm. 2 different time hydrochlorothiazide orally, blood pressure and blood and myocardial tissue ET-1 levels significantly decreased, blood, myocardial tissue NO of eNOS, eNOSmRNA levels were significantly increased, and regardless of the time of the perfusion. 3 different time hydrochlorothiazide orally, blood pressure and blood of rats and (or) myocardial tissue NO of eNOS, ET-1 levels peak time of eNOSmRNA have the advance, but did not disrupt the normal circadian rhythm, and not affected by the medication time.
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