不同种类降压药对血压变异性的影响

目的通过比较6种不同种类降压药(吲达帕胺、依那普利、缬沙坦、氨氯地平、美托洛尔、特拉唑嗪)对患者血压的影响,总结不同种类降压药对血压变异性的影响。方法对85例18⁶5岁确诊为原发性高血压(EH)的患者,分4个阶段服用常见6大类降压药:吲达帕胺(利尿剂)、依那普利(ACEI)、缬沙坦(ARB)、氨氯地平(钙离子拮抗药)、美托洛尔(β1受体阻断药)、盐酸特拉唑嗪(α阻滞剂)。采用无创性便携式动态血压监测仪,24小时动态血压测量及分析系统(简称:ABPM测量装置)对患者血压进行监测,调节血压(6∶0065岁确诊为原发性高血压(EH)的患者,分4个阶段服用常见6大类降压药:吲达帕胺(利尿剂)、依那普利(ACEI)、缬沙坦(ARB)、氨氯地平(钙离子拮抗药)、美托洛尔(β1受体阻断药)、盐酸特拉唑嗪(α阻滞剂)。采用无创性便携式动态血压监测仪,24小时动态血压测量及分析系统(简称:ABPM测量装置)对患者血压进行监测,调节血压(6∶00²2∶00)每20分钟测量1次,晚上每30分钟测量1次的对比试验,根据实验数据分析这6种药物对于实验对象的影响及不同药物对血压BPV的影响。结果吲达帕胺、缬沙坦和氨氯地平有降低24 h血压BPV的作用;依那普利、特拉唑嗪和美托洛尔有升高24 h血压BPV的作用。缬沙坦组用药后,使24 h收缩压BPV降低了(1.72±4.43)mmHg,24 h舒张压BPV降低了(0.68±1.29)mmHg,其降低的幅度远远大于其他药物组。吲达帕胺组用药后使24 h收缩BPV降低了(1.63±2.79)mmHg、24 h舒张压BPV降低了(0.24±1.80)mmHg,其降低幅度比缬沙坦组略小。氨氯地平降低24 h舒张压,其降低值为(-1.3±0.23)mmHg,其降低幅度要比缬沙坦和吲达帕胺小。依那普利组、特拉唑嗪和美托洛尔组的24 h血压BPV有一定程度的升高。结论 6种降压药对血压变异性的影响存在差异性。     

Synergistic effects of atenolol and amlodipine for lowering and stabilizing blood pressure in 2K1C renovascular hypertensive rats

AIM: To test the synergistic effects of atenolol and amlodipine on lowering blood pressure (BP) and reducing blood pressure variability (BPV) in 2-kidney, one-clip (2K1C) renovascular hypertensive rats. METHODS: Forty-eight 2K1C renovascular hypertensive rats were randomly divided into 6 groups. They were respectively given 0.8% carboxymethylcellulose sodium (control), atenolol (10.0 mg/kg), amlodipine (1.0 mg/kg), and combined atenolol and amlodipine (low dose: 5.0+0.5 mg/kg; intermediate dose: 10.0+1.0 mg/kg; high dose: 20.0+2.0 mg/kg). The drugs were given via a catheter in a gastric fistula. BP was recorded for 25 h from 1 h before drug administration to 24 h after administration. RESULTS: Compared with BP before medication, all 3 doses of combined atenolol and amlodipine significantly decreased the BP at 24 h after administration, except for the low dose on diastolic BP. Compared with the control group, all 3 doses of combined atenolol and amlodipine significantly reduced the average BP levels for the 24 h period after administration; furthermore, the high and intermediate doses also significantly decreased the BPV levels for the same period. The q values calculated by probability sum analysis for systolic and diastolic BP for the 24 h period after administration were 2.29 and 1.45, respectively, and for systolic and diastolic BPV for the same period they were 1.41 and 1.60, respectively. CONCLUSION: There is significant synergism between atenolol and amlodipine in lowering and stabilizing BP in 2K1C renovascular hypertensive rats.     

Blood pressure variability and baroreflex sensitivity are not different in spontaneously hypertensive rats and stroke-prone spontaneously hypertensive rats

AIM: To demonstrate and compare hemodynamic phenotypes of blood pressure (BP), blood pressure variability (BPV) and baroreflex sensitivity (BRS) in genetic hypertensive rats. METHODS: BP was recorded continuously in conscious, freely moving rats using a computerized technique. BPV was expressed as the standard deviation of beat-to-beat BP values during a 1-h period. BRS was determined by measuring the heart period prolongation in response to the elevation in BP produced by an intravenous injection of phenylephrine. RESULTS: Body weight and heart period were not different between spontaneously hypertensive rats (SHR) and stroke-prone spontaneously hypertensive rats (SHR-SP) at the age of 15 weeks. The BP level was markedly higher in SHR-SP than SHR, whereas there were no significant differences in BPV and BRS. Quantitatively, systolic, diastolic and mean BP were significantly elevated by 36.9%, 42.9% and 39.5%, respectively, in SHR-SP compared with SHR (P < 0.01). However, their variabilities were elevated only by 14.0%, 0.4% and 10.1%, respectively, without statistical significance (P > 0.05). CONCLUSION: BPV and BRS were not changed in parallel with the BP alterations in SHR and SHR-SP.     

Effects of long-term treatment with candesartan on organ damages in sinoaortic denervated rats

The study was designed to observe the effects of long-term treatment with candesartan cilexetil (candesartan) on blood pressure (BP), blood pressure variability (BPV), baroreflex sensitivity (BRS) and end-organ damage (EOD) in sinoaortic denervated (SAD) rats. Candesartan was mixed in rat chow at an estimated dose of 3 mg/kg/day. After 12 weeks of drug administration, rats were instrumented to determine BP, BPV and BRS in conscious state. Organ damage was estimated by observation of morphologic changes. When compared with sham-operated rats, SAD rats exhibited increased BPV, decreased BRS, and normal BP and plasma angiotensin II level. Left ventricular and aortic hypertrophies and renal lesion were found in SAD rats. Candesartan significantly decreased BP and BPV, ameliorated impaired BRS, increased plasma angiotensin II level and obviously diminished the EOD in SAD rats. Multiple-regression analysis shows that decrease in left ventricular hypertrophy was mainly related to decrease in systolic BPV. Decrease in aortic hypertrophy was mainly determined by increase in BRS and decrease in systolic BP. Amelioration in renal lesion was predicted by increase in BRS and decrease in systolic BPV. BRS was the most important determinant for renal lesion and aortic hypertrophy in SAD rats. In addition, plasma angiotensin II level was higher in candesartan-treated rats. In conclusion, long-term treatment with candesartan prevented SAD-induced organ damage. Restoration of arterial baroreflex function, decrease in BPV, and blockade of activated renin-angiotensin system may contribute to the organ protective action of candesartan in SAD rats.     

Synergism of hydrochlorothiazide and nitrendipine on reduction of blood pressure and blood pressure variability in spontaneously hypertensive rats

AIM: To investigate the possible synergism of hydrochlorothiazide and nitrendipine on reducing both blood pressure (BP) and blood pressure variability (BPV) in spontaneously hypertensive rats (SHR). METHODS: Seventy animals were randomly divided into seven groups. The doses were 5 and 10 mg/kg for nitrendipine, 10 and 20 mg/kg for hydrochlorothiazide and 10 + 5, 20 + 10 mg/kg, respectively, for the combination of these two drugs and 0.8% carboxymethylcellulose as control. The drugs were given via a catheter of gastric fistula. BP was then continuously recorded for 5 h from 1 h before drug administration to the end of 4th hour after drug administration, in conscious and freely moving rats. RESULTS: The effects on both BP and BPV reduction of the combination of hydrochlorothiazide and nitrendipine were greater than the single drug in SHR. The two drugs possessed an obvious synergism on both systolic blood pressure (q = 1.79 with small dose and q = 1.23 with large dose) and systolic blood pressure variability reduction (q = 1.79 with small dose and q = 1.39 with large dose) in SHR. CONCLUSION: The present work clearly demonstrated that there was a synergistic effect between hydrochlorothiazide and nitrendipine in lowering and stabilizing BP in SHR.     

胰高血糖素肽1对糖尿病伴高血压患者血压变异性的影响

【摘要】目的 探讨胰高血糖素肽1（GLP-1）对2型糖尿病伴高血压患者血压变异性（BPV）的影响。方法 选取糖尿病伴高血压患者120例,使用GLP-1对其进行治疗,检测患者使用前及使用6个月后体质指数（BMI）、空腹血糖、糖化血红蛋白、血清肌酐、血脂等,并进行24h动态血压监测,得到短时BPV。比较治疗前后的相关指标。结果 使用GLP-1后6个月,患者空腹血糖（mmol/L :7.12±0.64vs9.19±2.78）、糖化血红蛋白（%:7.00±0.14vs8.28±1.32）、BMI（kg/m2: 19.30±3.24vs24.50±4.53）较治疗前下降（P<0.05）,达到控制目标。24h收缩压（mmHg :135.02±16.57vs139.52±15.60）、白昼收缩压（mmHg:132.50±14.60vs136.44±14.24）、24h收缩压变异性（mmHg:12.20±1.44vs12.73±1.66）、白昼收缩压变异性（mmHg:11.11±1.48vs11.74±1.52）、白昼舒张压变异性（mmHg:7.03±1.42vs7.43±1.45）也降低（P<0.05）。结论 GLP-1可降低糖尿病伴高血压患者的BPV。     

Blood pressure variability and organ damage

1. Blood pressure variability (BPV) is expressed as the standard deviation of the average blood pressure (BP). Blood pressure variability is increased in hypertensive patients and animals. However, BPV is not necessarily related to the BP level. 2. For nearly any level of 24 h mean BP, hypertensive patients in whom the BPV is low have a lower prevalence and severity of organ damage than patients in whom the 24 h BPV is high. This observation has been confirmed further in spontaneously hypertensive rats with direct pathological analysis for organ damage. 3. In sinoaortic-denervated (SAD) rats, 24 h average BP is normal and BPV is markedly increased. Myocardial damage, renal lesions and vascular remodelling are seen in these animals 4 weeks after SAD. 4. Haemodynamic effects and activation of the renin- angiotensin system are hypothesized to contribute to organ damage induced by increased BPV. 5. Blood pressure variability is of potential importance in antihypertensive therapy.     

利尿剂协同ACE抑制剂降压作用的实验研究

目的研究利尿剂氢氯噻嗪与ACE抑制剂依那普利联合对自发性高血压大鼠降低血压及血压波动性的协同作用,评价两药不同比例配伍时的协同作用效果。方法采用清醒动物血压监测技术,监测自发性高血压大鼠分别通过胃瘘管给予0.8%的羧甲基纤维素钠(CMC)、氢氯噻嗪(10mg/kg)、依那普利(2,4,8mg/kg)、氢氯噻嗪和依那普利混悬液(10+2、10+4、10+8mg/kg)后血压及血压波动性的变化。结果与对照组比较氢氯噻嗪和依那普利合用时可以明显的降低血压及血压波动性。大剂量合用时降低收缩压55mmHg(1mmHg=0.133kPa),大于两药单独使用时的降压幅度。q值在氢氯噻嗪+依那普利10+4mg/kg时最大。结论利尿剂与ACE抑制剂合用对降低血压及血压波动性具有明显的协同作用,氢氯噻嗪:依那普利为5:2时协同作用最为明显。     

Effects of nine antihypertensive drugs on blood pressure variability in sinoaortic-denervated rats

AIM: The present work was designed to investigate the effects of nine commonly used antihypertensive drugs on blood pressure (BP) and blood pressure variability (BPV) in conscious sinoaortic-denervated (SAD) rats. METHODS: Seventy-two SAD rats were randomly divided into nine groups. They were respectively given nifedipine 3 mg/kg, nitrendipine 5 mg/kg, amlodipine 1 mg/kg, clonidine 10 mug/kg, prazosin 0.5 mg/kg, atenolol 20 mg/kg, telmisartan 20 mg/kg, hydrochlorothiazide 40 mg/kg or captopril 50 mg/kg. The drugs were given via a catheter previously implanted into the stomach. BP was recorded for 5 h from 1 h before drug administration to 4 h after drug administration in conscious, freely moving rats. RESULTS: It was found that all these nine drugs significantly decreased BP in SAD rats. Six of these drugs (nifedipine, nitrendipine, amlodipine, clonidine, prazosin and atenolol) significantly decreased BPV in SAD rats, but the remaining three drugs did not. Clonidine and atenolol increased the heart period and the others did not. No drugs affected the heart period variability. CONCLUSION: Among nine antihypertensive drugs from different classes, calcium antagonists and sympathetic inhibitors decreased BPV in SAD rats.     

血压波动性在尼群地平和阿替洛尔联合治疗自发性高血压大鼠的器官保护中的重要性

AIM: To study the importance of reduction of blood pressure variability (BPV) in the organ protection of long-term treatment with combination of nitrendipine and atenolol, which was abbreviated as Nile, in spontaneously hypertensive rats (SHR). METHODS: Combination of nitrendipine (10 mg/kg/d) and atenolol (20 mg/kg/d) was given in SHR chow for 12 weeks. Blood pressure (BP) was then recorded during 24 h in conscious state. After the determination of baroreflex sensitivity (BRS), rats were killed for organ-damage evaluation. RESULTS: Long-term treatment with Nile significantly decreased BP and BPV, ameliorated impaired BRS, and obviously diminished end-organ damage in SHR. The indices of left ventricular and aortic hypertrophy, and glomerulosclerosis score were all positively related to BP and BPV, and negatively related to BRS in untreated and Nile-treated SHR. Multiple-regression analysis showed that decrease in left ventricular and aortic hypertrophy was mainly related to the decrease in systolic BPV, and amelioration in renal lesion was mainly determined by increase in BRS. CONCLUSION: Long-term treatment with Nile possessed obvious organ protection in SHR. Besides the BP reduction, the decrease in BPV and the restoration of BRS may importantly contribute to this organ protection.