| Objective:The biorhythm is the most universal phenomenon,which can cause the biological energy to adapt the surrounding conditions well.Characteristics of human biorhythm of blood pressure(BP),characterized with higher level in daytime and lower level at night time.It is believed that,abnormal circadian rhythm of BP can increase the risk of heart,brain,kidney and other organs damage,as well as increase the incidence and mortality of cerebral hemorrhage,cerebral infarction,myocardial infarction,arrhythmia.Circadian rhythm of BP can be under the influence of a variety of neuro-humoral key points,among which renin-angiotensin-aldosterone system(RAAS)is extremely important.During the recent years,the studies suggested that the local RAAS of the kidney was perfect.Urinary angiotensinogen(AGT)level was positively correlated with the activity of intrahepatic AGT and angiotensin II(Ang II).So urinary AGT,Ang II and aldosterone might be important indicators which reflected the activity of RAAS in kidney.This study collected the urine of spontaneously hypertensive rats(SHR)on the same day at different time points(06:00,12:00,18:00,24:00)to study the effect of feeding spironolactone at different time(morning or evening)on the activities or levels of AGT,renin,Ang II,aldosterone and other active substances in the urine and circadian rhythm of SHR.Then we measured and compared among the different groups.Methods:30 healthy and clean 10-week-old male SHRs(body weight:250-300g),fed at the Animal Center of Hebei General Hospital,were subjected to conform feeding for one week before usage of spironolactone,making them suitable the surrounding condition.30 SHRs were randomlydivided into three groups(10 SHRs in each group): SHRs feeding with spironolactone at 07:00(group M),SHRs feeding with spironolactone at 19:00(group N),SHRs feeding with physiological saline as control group(group C).Every day group M and group N were treated with spironolactone 20mg/Kg,while group C were given equal volume of physiological saline once a day.Feeding according to the above scheme lasted for 8 weeks.The systolic blood pressure(SBP)of three groups of SHRs were respectively measured before feeding spironolactone,feeding spironolactone 4 weeks,feeding spironolactone 8 weeks,with a noninvasive rat tail sphygmomanometer.At the8 th week of feeding,the body weight of each group SHRs were weighed and urine of each group SHRs were collected at different time points(06: 00,12:00,18: 00,24: 00)of the same day within 24 hours.The levels of AGT,Ang?,aldosterone and renin in urine of each group were detected by Enzyme-linked immunosorbent assay.After the collection of urine,the SHRs of each group were sacrificed and the heart was removed.Weigh the mass of the whole heart and then separate the left ventricle to weigh the left ventricular mass(LVM),then calculated the heart weight index(HWI).Variance analysis was used to determine whether there was a statistically significant difference in AGT,Ang II,aldosterone,renin levels among the groups(P<0.05).Cosine fitting method and zero amplitude test were applied to evaluate whether there were circadian rhythms of the above indicators.Results:1 AGT,Ang?,aldosterone and renin levels in urine of SHRs:The 24-hour mean levels of AGT,Ang? and aldosterone in urine of group M and group N were significantly lower than those in group C(P<0.01),while there were no significant difference in group M and group N(3comparative indicators were respectively: P=0.232,P=0.882,P=0.057).The24-hour mean levels of renin in urine of group M and group N were significantly higher than those in group C(P<0.01),while the difference between group M and group N was not statistically significance(P=0.347).2 At baseline,there was no significant difference among the SBP of eachgroup(P>0.05).When feeding spironolactone 4 weeks and 8 weeks,the SBP of M group and group N were significantly decreased(P<0.01).The difference between M group and N group was not statistically significance(P=0.142,P=0.154,4 weeks and 8 weeks,respectively).3 The result of the LVM and HWI level in the three groups were shown as below.The LVM and HWI of group M and group N were significantly lower than those of group C(P<0.01),but there was no significant difference between group M and group N(P=0.247,P=0.822).4 The AGT,Ang II,aldosterone,renin and other active substances' time-biology characteristics of all the three groups: the RAAS indicators of SHRs urine showed a circadian rhythm characteristic.The peak values of AGT,Ang II,aldosterone and renin in the urine of group C occured in the order of00:36,07:46,02:11,07:05.In group M,the peak values of the above indexes occured in the order of 03:12,08:55,03:05,12:07.The peak values of the above indexes in group N appear in the order of 06:03,10:13,03:43,19:24.Compared with group C,the peak time of group M and group N were delayed,and the peak time of group N was delayed compared with group M.Conclusions:1 The average concentration of renin in SHR urine increaseed in group M and group N,compared with group C.But the average concentration of AGT,Ang II and aldosterone were all decrease.2 The SBP of SHRS was reduced when administrating spironolactone both at early time and at late time.There was no significant difference on SBP when administrating spironolactone at different time.3 Administrating spironolactone reduced the left ventricular mass and heart weight index of SHRs.4 The concentration of AGT,Ang II,aldosterone and renin in the urine of SHR rats showed a typical circadian rhythm characteristic in three groups.The rhythm peak of above indicators delayed in a certain degree when administering spironolactone at different time.The rhythm peak of above indicators delayed in group N compared with group M.It is suggested thatadministering spironolactone at different time can affect the temporal biological characteristics of the active components of RAAS in urine of SHR. |
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