Establishment of a Rat Model of Hypotension Induced by Reserpine

ZHANGXuan, WANGCi, ZHANGZeyu, ZHANGPeipei, RENQiu'an, WANGXianliang, MAOJingyuan

Acta Academiae Medicinae Sinicae ›› 2023, Vol. 45 ›› Issue (4) : 533-540.

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Acta Academiae Medicinae Sinicae ›› 2023, Vol. 45 ›› Issue (4) : 533-540. DOI: 10.3881/j.issn.1000-503X.15376
Original Articles

Establishment of a Rat Model of Hypotension Induced by Reserpine

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Abstract

Objective To determine the optimal dosage and intervention duration of reserpine to establish a rat model of hypotension.Methods According to the body weight and systolic blood pressure (SBP),60 male Wistar rats were assigned to six groups (n=10),including a control group and five observation groups with different doses.The control group was administrated with 10 ml/kg 0.5% sodium carboxymethyl cellulose solution,and the observation groups with 0.016,0.032,0.064,0.128,and 0.160 mg/kg reserpine suspensions,respectively.All the groups were administrated by gavage twice a day,and the body weights of rats were monitored daily.SBP and heart rate (HR) were measured before modeling and 1-6 weeks after administration.After 6 weeks of administration,the blood samples of inner canthus were collected.The levels of lactate dehydrogenase (LDH),creatine kinase MB isoenzyme (CK-MB),alanine aminotransferase,aspartate aminotransferase (AST),serum creatinine,and blood urea nitrogen (BUN) were measured by an autoanalyzer.Three rats in each group were randomly selected for observation of the changes in SBP after drug withdrawal and the rest rats were sacrificed for measurement of the levels of norepinephrine and dopamine in the brain.Results Compared with the control group,different doses of reserpine lowered the SBP of rats (F=28.492,P<0.001).The decline in SBP increased in a concentration-dependent manner.SBP reached the lowest value after 1 week,rose slightly later,and was stable after 3 weeks of administration.There was no significant difference in SBP between 0.016 mg/kg reserpine group and the control group after the 5th week (P>0.05).The SBP levels of rats in 0.032,0.064,0.128,and 0.160 mg/kg reserpine groups showed no significant difference between each other (P=0.204) and were lower than that in the control group (all P<0.001).One week after drug withdrawal,the SBP of rats in the observation groups rose to the baseline level and remained stable.HR showed similar changes among groups,first increasing and then decreasing.There was no significant difference in HR among different groups at the same time point (F=0.922,P=0.475).Compared with the control group,reserpine of different doses reduced the norepinephrine content in the hippocampus (all P<0.001),and 0.128 mg/kg (P=0.045) and 0.160 mg/kg (P=0.042) reserpine lowered the dopamine level in the striatum,which showed no significant differences between different reserpine groups(P=0.343,P=0.301).The levels of LDH,CK-MB,and BUN in the serum increased with the increase in reserpine concentration,and the levels of LDH (P=0.001),CK-MB (P=0.020),AST (P=0.007),and BUN (P=0.001) in the 0.160 mg/kg reserpine group were significantly different from those in the control group.Conclusions The rat model of hypotension can be induced by gavage with reserpine.The gavage with reserpine at a dose of 0.032 mg/kg,twice a day for three consecutive weeks is the optimal scheme for the modeling.After the model establishment,continuous administration is essential to maintain the hypotension.

Key words

hypotension / animal model / reserpine

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ZHANG Xuan , WANG Ci , ZHANG Zeyu , et al . Establishment of a Rat Model of Hypotension Induced by Reserpine[J]. Acta Academiae Medicinae Sinicae. 2023, 45(4): 533-540 https://doi.org/10.3881/j.issn.1000-503X.15376

References

[1]
陈灏珠. 心脏病学—心血管内科学[M]. 北京: 人民卫生出版社, 2016.
[2]
Afari N, Buchwald D. Chronic fatigue syndrome:a review[J]. Am J Psychiatry, 2003, 160(2):221-236.DOI:10.1176/appi.ajp.160.2.221.
[3]
Barrett-Connor E, Palinkas LA. Low blood pressure and depression in older men:a population based study[J]. BMJ, 1994, 308(6926):446-449.DOI:10.1136/bmj.308.6926.446.
To determine if an association exists between low blood pressure and depressive symptoms in older men living in the community.Cross sectional, population based study.Town of Rancho Bernardo, California, United States.846 men aged 60-89 years. Comparisons between hypotensive, normotensive, and hypertensive groups were limited to 594 men not taking drugs for hypertension.Mean scores on Beck depression inventory and prevalence of scores > or = 13.Men with diastolic blood pressure < 75 mm Hg had significantly higher depression scores (mean scores 6.35 v 4.96; P < 0.001) and more categorical depression (7.6% v 1.8% with scores > or = 13; P < 0.01) than men with diastolic blood pressure levels between 75 and 85 mm Hg. Men with diastolic blood pressure levels > 85 mm Hg had higher depression scores than men with intermediate blood pressure levels (mean scores 5.85 v 4.96; P < 0.05). Men with diastolic hypotension scored significantly higher on both affective and somatic item subscales of the Beck depression inventory and on individual measures of fatigue, pessimism, sadness, loss of appetite, weight loss, and preoccupation with health. Low diastolic blood pressure was a significant predictor of both mean depression score and prevalence of categorical depression, independent of age and change in weight since the baseline visit. The presence of several chronic diseases was associated with depressed mood and higher blood pressure but not with low blood pressure.The association of relatively low diastolic blood pressure with higher depressive symptom scores and rates of categorical depression was independent of age or weight loss. Since fatigue is a prominent symptom of depression, any association of low blood pressure with fatigue could reflect depressive disorders or clinically important depression.
[4]
Duschek S, Schandry R. Reduced brain perfusion and cognitive performance due to constitutional hypotension[J]. Clin Auton Res, 2007, 17(2):69-76.DOI:10.1007/s10286-006-0379-7.
This review article includes a systematic evaluation of the empirical data concerning deficits in mental ability, brain perfusion, and cerebral functioning due to chronically low blood pressure. A number of studies have provided strong evidence for reduced cognitive performance in hypotension, particularly in the domains of attention and memory. EEG studies have demonstrated that the hypotension-related poorer mental ability is also reflected in diminished cortical activity. Contrary to convention, more recent research has suggested a deficient regulation of cerebral blood flow in persons with low blood pressure. In addition to reduced tonic brain perfusion, studies demonstrated insufficient adjustment of blood flow to cognitive requirements. Altogether, these findings suggest that more attention should be allocated to chronic hypotension in both research and clinical practice.
[5]
罗德, 陈少雄. 七味平衡升压汤联合西药治疗原发性低血压病的疗效观察[J]. 中国民族民间医药, 2018, 27(13):86-88.
[6]
朱林章. 维生素B1、甲钴胺联合参松养心胶囊治疗原发性低血压病的探讨[J]. 中国医学创新, 2009, 6(36):53.DOI:10.3969/j.issn.1674-4985.2009.36.032.
[7]
吕耀成. 七味平衡升压汤联合盐酸米多君篇治疗原发性低血压病41例[J]. 中医研究, 2019, 32(8):25-28.DOI:10.3969/j.issn.1001-6910.2019.08.11.
[8]
Liu SQ, Fung YC. Relationship between hypertension,hypertrophy,and opening angle of zero-stress state of arteries following aortic constriction[J]. J Biomech Eng, 1989, 111(4):325-335.DOI:10.1115/1.3168386.
Examination of changes occurring in the zero-stress state of an organ provides a way to study cellular growth in the organ due to change of physical stresses. The zero-stress state of the aorta is not a tube. It is a sector with an opening angle that varies with the location on the aorta and changes with cellular remodeling. Blood vessel remodeling can be induced by imposing a constriction on the abdominal aorta by a metal clip (aortic banding), which causes an increase of blood pressure, hypertrophy of the aortic wall, and large change of opening angle. The correlation of the opening angle with the blood vessel wall thickness and blood pressure changes in rat’s aorta due to aortic banding is presented in this report. The opening angle changes daily following the aortic banding. Blood pressure rises in vessels of the upper body, but that in the lower body decreases at first and then rises to an asymptotic value. Blood vessel wall thickness increases in rough proportion to blood pressure. Vessel diameter changes also. But the most dramatic is the course of change of the zero-stress state. Typically, the time to reach 50 percent of asymptotic hypertrophy of blood vessel wall thickness is about 3–5 days. The corresponding time for blood pressure is about 7 days. The opening angle of the zero-stress state, however, increases rapidly at first, reaches a peak in about 2 to 4 days, then decreases gradually to a reduced asymptote. The exact values of the time constants depend on the location along the aortic tree. In general, the course of change of residual strain is very different from those of the blood pressure and the blood vessel wall thickness.
[9]
秦彩玲, 刘婷, 张毅, 等. 桂枝汤对大鼠血压双向调节作用及其有效部位探讨[J]. 中国实验方剂学杂志, 2001, 7(4):20-23.DOI:CNKI:SUN:ZSFX.0.2001-04-009.
[10]
杨路, 吴春晓, 陈莹, 等. 针刺手三阴经原穴对高、低血压模型大鼠经穴特异性的影响[J]. 广州中医药大学学报, 2016, 33(3):334-338.DOI:10.13359/j.cnki.gzxbtcm.2016.03.013.
[11]
田原. 人参超微粉及水提物对大鼠实验性低血压的升压作用研究[D]. 吉林: 吉林大学, 2018.
[12]
杨国为, 周岩, 林红华. 原发性低血压病紧张刺激研究分析[J]. 福建医药杂志, 1995, 17(6):66.
[13]
Covassin N, De Zambotti M, Cellini N, et al. Nocturnal cardiovascular activity in essential hypotension:evidence of differential autonomic regulation[J]. Psychosom Med, 2012, 74(9):952-960.DOI:10.1097/PSY.0b013e318272db69.
Essential hypotension represents a form of chronic low blood pressure (BP) not explained by medical or orthostatic conditions. The pathogenesis of essential hypotension may involve sympathetic hypoactivation and other forms of autonomic dysregulation. The aim of the current study was to investigate autonomic and cardiovascular activity during sleep in individuals with essential hypotension.A case-control study was conducted in 14 individuals with essential hypotension (mean [standard error] = 23.4 [0.6] years, all women) and 14 controls (mean [standard error] age = 22.2 [0.4] years, all women). The following measures were collected over a night of sleep: BP, heart rate (HR), stroke volume, cardiac output (CO), preejection period (PEP), total peripheral resistance, and time-domain measures of HR variability.Hypotensive participants had consistently lower BP, HR, and CO than did normotensives. Cardiac autonomic variables revealed enhanced parasympathetic tone (proportion of adjacent normal-to-normal intervals that differed in length by more than 50 milliseconds = 40.8 [6.3] versus 23.4 [4.5], p =.03) and reduced sympathetic drive in hypotensives (PEP = 99.4 [3.6] versus 86.1 [4.3], p =.02). Analysis of temporal profiles showed that HR, stroke volume, and CO decreased throughout the night in both groups, whereas PEP and HR variability increased. Unlike controls, BP remained essentially unchanged in hypotensives, as the decrease in CO was counterbalanced by a parallel rise in total peripheral resistance.These findings suggest that nocturnal cardiac sympathetic withdrawal combined with vagal hyperactivity is a characteristic of the autonomic regulation in essential hypotension.
[14]
中老年医学会高血压分会, 中华医学会心血管病学分会, 中国医师协会高血压专业委员会, 等. 复方利血平氨苯蝶啶片(0号)临床应用中国专家共识2021版[J]. 中华老年多器官疾病杂志, 2021, 20(9):5.DOI:10.3969/j.issn.1007-5410.2021.05.005.
[15]
Willner P. The validity of animal models of depression[J]. Psychopharmacology, 1984, 83(1):1-16.DOI:10.1007/BF00427414.
Eighteen animal models of depression are reviewed in relation to three sets of validating criteria. Of the 18 models, five could only be assessed for predictive validity, seven could be assessed for predictive and face validity, and six could potentially have predictive, face and construct validity. Some traditional models (reserpine reversal, amphetamine potentiation) are rejected as invalid; the models with the highest overall validity are the intracranial self-stimulation, chronic stress and learned helplessness models in rats, and the primate separation model.
[16]
Carlsson A, Lindqvist M, Magnusson T. 3,4-dihydroxypheylalanine and 5-hydroxy-tryptophan as reserpine antagonitst[J]. Nature, 1957, 180(4596):1200.DOI:10.1038/1801200a0.
[17]
高雪松, 王永志, 李丽, 等. 利血平致抑郁样啮齿类动物模型的研究进展[J]. 实验动物学, 2017, 34(2):57-60.
[18]
Ahmed-Farid OA, Taha M, Bakeer RM, et al. Effects of bee venom and dopamine-loaded nanoparticles on reserpine-induced parkinson's disease rat model[J]. Sci Rep, 2021, 11(1):21141.DOI:10.1038/s41598-021-00764-y.
Parkinson's disease (PD) is a progressive chronic neurodegenerative condition characterized by the loss of dopaminergic neurons within the substantia nigra. Current PD therapeutic strategies are mainly symptomatic and can lead to motor complications overtime. As a result, alternative medicine may provide an effective adjuvant treatment for PD as an addition to or as a replacement of the conventional therapies. The aim of this work was to evaluate the effects of Bee Venom (BV) and dopamine (DA)-loaded nanoparticles in a reserpine-induced animal model of PD. After inducing PD with reserpine injection, different groups of male rats were treated with L-Dopa, BV, DA-nanoparticles. Our findings showed that BV and DA-nanoparticles administration restored monoamines, balanced glutamate/GABA levels, halted DNA fragmentation, decreased pro-inflammatory mediators (IL-1β and TNF-α), and elevated anti-inflammatory mediators (PON1) and neurotropic factor (BDNF) levels in comparison with conventional therapy of PD. Furthermore, in a reserpine-induced PD rat model, the ameliorative effects of BV were significantly superior to that of DA-nanoparticles. These findings imply that BV and DA-nanoparticles could be useful as adjuvant treatments for PD.© 2021. The Author(s).
[19]
李亚欢, 张冬梅, 王淑艳, 等. 脾虚证动物模型研制概况[J]. 中医药导报, 2019, 25(1):100-102.
[20]
王璇. 低血压症的中医证候-方药分布特点及临床观察[D]. 济南: 山东中医药大学, 2015.
[21]
李艳芳, 师树田. 受体激动剂与阻滞剂在心血管病的临床应用[M]. 北京: 人民军医出版社, 2014.
[22]
王庭槐. 生理学[M]. 北京: 人民卫生出版社, 2018.
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