| Objective: Biological rhythms are a universal phenomenon in living organisms. In humanbeings, various kinds of vital phenomena show some degree of biological rhythms and the most frequent was the carcadian rhythm. Recently, it has been found that the abnormal rhythms of blood pressure not only increase the risks of target organs damage but also increase the cardiovascular morbility and mortality. It would be very important that to get well known of the chronobiology characters of blood pressure and relative influential factors.The regulation of blood pressure is a complicated process, the renin-angiotensin system (RAS), which is an essential part to keep stable of the body internal environment and to accommodate blood pressure, moisture and electrolyte, may plays important roles in it. Studies have confirmed that the levels of plasma renin activity (PRA), angiotensin -II (Ang II) and angiotensin converting enzyme (ACE) show circadian rhythm, and their chronobiology characters have closely correlation to the circadian rhythm of cardiovascular diseases. Nifedipine has been introduced as a kind of anti-hypertension drugs for more than half one century, which is more effective on anti-hypertension areas and enable decreasing the incidence and mortality of cardiovascular events. So, this type calcium-channel blocker has been played an important role in anti-hypertensive field. Therefore, in this study, we investigated the circadian rhythm of RAS in the plasma and myocardium in rats and the effects of nifedipine on the circadian rhythm of RAS.Methods: The experiment was carried out in sixty-four age-matched male Sprague-Dawlay rats (with body weight 250-300g). After one week's free-running period in natural light-dark cycles, the rats were housed at 22±2°C and free access to food and water. They were divided randomly into two groups: the control group rats were designated as "N group"; the experimental group rats (treated with nifedipine 6mg/Kg) were designated as "T group". There were 32 rats in each group, which was divided into 4 sub-groups (with 8 rats in each one). Each group was maintained in same condition for 4 weeks before the experiment. Animal experiments were conducted in accordance with guidelines of Hebei Geriatric Institute.For the determination of the diurnal pattern of PRA, ACE, Ang II in serum and myocardial tissue, as well as AT-1mRNA expressions in rats'myocardial tissue, the rats were sacrificed every 6 hours (with one sub-group at 02:00, 08:00, 14:00 and 20:00, respectively) by operating on chest and the indices above were measured. Cosinor fitting analysis and zero amplitude tests were introduced to analyze the chronobiological features of RAS in every group. The compare of circadian values between two groups was managed based on student's t test and p<0.05 was defined as statistically different borderline.Results: 1. The level of PRA in serum was higher in T group than that in N group (p<0.05). The levels of ACE and Ang II in serum were not significantly difference between the two groups (p>0.05).2. The levels of Ang II in myocardial tissue were not significantly difference between the two groups (p>0.05). But, the levels of AT-1mRNA in myocardial tissue were lower in T group than those in N group by using t-test (p<0.05).3. Based on cosinor fitting analysis and zero amplitude test, circadian rhythms were found in both groups, and the curves and characteristic values of serum level of PRA, Ang II and ACE were obtained respectively. The phases of peak value of PRA, Ang II and ACE in serum of N group occurred in turn were 00:48,05:27,01:32, of T group occurred in turn were 21:58, 01:39, 22:04, which were somewhat earlier than those in N group. Furthermore, the amplitudes of vibration of PRA in serum were augmented in T group, but the amplitudes of vibration of Ang II and ACE in the two groups were without any difference.4. Based on cosinor fitting analysis and zero amplitude tests, Ang II and AT-1mRNA in myocardial tissue of the two groups showed typical circadian rhythms. The phase of the peak value of Ang II and AT-1mRNA in myocardium of the rats in N group occurred at 04:55 and 09:34, respectively, and of T group occurred at 01:57 and 02:03, which were earlier than those in N group. Furthermore, the amplitudes of vibration of Ang II and AT-1mRNA in myocardial tissue were also augmented in T group.Conclusion: 1. The levels of PRA, Ang II, ACE and AT-1mRNA in serum and/or myocardial tissue of the two groups show typical circadian rhythms.2. Nifedipine might increase the levels of PRA. But the levels of ACE, Ang II in the serum and in the myocardial tissue were not changed in the two groups. In addition, the expression of AT-1mRNA in myocardial tissue was down-regulated with nifedipine-treated schedule.3. Nifedipine could change the circadian features of the PRA, Ang II, ACE and AT-1mRNA in serum and/or myocardial tissue, including the alteration of the peak phase and the amplitudes of vibration.
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