The effects of beta-adrenergic blocking agents on blood lipid levels

This review examines the effects of beta-adrenergic blocking agents on blood lipids. These agents have been effective in the treatment of angina and hypertension and in the reduction of recurrence of ischemic cardiac disease, such as myocardial infarction. Many beta blockers, however, have an adverse effect on blood lipids, especially by reducing high-density lipoprotein (HDL) cholesterol and increasing triglycerides. One result is an unfavorable influence on the cholesterol ratio (expressed either as low-density lipoprotein [LDL]/HDL or total cholesterol/HDL). These cholesterol parameters have been shown to have a strong influence on coronary heart disease (CHD) risk. Studies have shown that antihypertensive therapy has reduced the incidence of cerebrovascular disease but, in many instances, has not reduced the incidence of CHD. A hypothesis for this lesser effect on coronary disease is that antihypertensive agents may be adversely affecting blood lipids. Thus, while one major risk factor for CHD is reduced, another may be somewhat enhanced. Pharmacologic properties of some beta blockers such as peripheral alpha blockade (e.g., with labetalol) or intrinsic sympathomimetic activity (ISA) (e.g., with pindolol) may counteract some of these negative lipid effects. An investigational beta blocker, bevantolol, which will be marketed shortly in the United States, has been effective in antihypertensive therapy. Bevantolol has been shown to lower LDL cholesterol and not adversely affect HDL cholesterol; in this way, bevantolol favorably influences the serum lipoprotein profile. Whether this effect will have clinical significance remains to be seen.     

Comparison of the efficacy of atenolol and its combination with slow-release nifedipine in chronic stable angina

Summary There is still uncertainty of whether combined therapy with a beta-blocker and calcium-channel antagonist provides additive or synergistic clinical benefits in most patients with stable angina pectoris. The comparative antianginal effect of atenolol 50 mg and atenolol 50 mg and slow-release nifedipine (20 mg) twice a day was assessed in 27 patients with chronic stable angina in a randomized, double-blind, crossover study. After a 4 week run-in period on atenolol, patients were randomly allocated to receiveeither atenolol aloneor its combination with nifedipine and then crossed over to the alternative treatment for a further 4 weeks. Symptom-limited exercise treadmill tests were performed according to the Naughton protocol. The major endpoints in this study were (a) exercise time to pain; (b) exercise time to 1 mm ST depression; (c) total exercise time; (d) maximal ST-segment depression; (e) number of anginal attacks; and (f) nitrate consumption. The preexercise systolic blood pressure was lower on the combination treatment than on atenolol alone, but heart rate was lower on atenolol compared with the combination treatment. There was no difference in the systolic blood pressure at the onset of pain or at 1 mm ST depression, while heart rate was lower on both occasions with atenolol compared to the combination treatment. There was no difference between the two treatments in terms of the rate-pressure product at the onset of pain or at 1 mm ST depression. Twice as many patients experienced pain later with the combination treatment than with atenolol alone. There was no difference for the time without ST segment depression, maximal exercise time, number of anginal attacks, nitrate consumption, and side effects between the treatments. These data suggest that, apart from the time of onset of mild pain, the combination treatment of slow release nifedipine (20 mg) and atenolol (50 mg) twice a day is no better than atenolol alone in patients with stable angina pectoris. It is uncertain whether a higher titrated dose of nifedipine combined with atenolol would have produced the same results.     

Differential effects of nebivolol and atenolol on transmitral diastolic filling parameters in patients with essential hypertension

INTRODUCTION: Impaired left ventricular (LV) diastolic relaxation, detected by pulsed Doppler echocardiography, is predictive of a higher incidence of major cardiovascular events in hypertensive patients. An improvement in LV diastolic function is an important goal of treatment. However, treatment of LV diastolic dysfunction remains empirical. The objective of our study was to compare the short-term effects of nebivolol and atenolol on Doppler diastolic filling parameters in hypertensive patients. METHODS: A total of 32 patients with mild-to-moderate hypertension were enrolled in the study. The patients were randomly assigned to receive treatment with either nebivolol (5 mg/day) or atenolol (50 mg/day) for 1 month. Diastolic filling parameters, with pulsed-wave Doppler transmitral flow velocities, were measured 1 day before and 1 month after treatment. RESULTS: Compared with baseline, both agents significantly decreased heart rate and blood pressure. However, there was no significant difference in pre-and post-treatment values between the nebivolol and atenolol groups. Both drugs significantly improved LV transmitral flow measured by early diastolic flow/atrial contraction signal (E/A) ratio, decreased deceleration time (DT) and isovolumetric contraction time (IVRT), but post-treatment improvement in E/A, DT and IVRT values was more significant with nebivolol compared with atenolol (P=0.05, P=0.05 and P=0.003, respectively). CONCLUSIONS: Although treatment with nebivolol or atenolol results in improved LV transmitral diastolic function filling parameters (E/A ratio, IVRT and DT), nebivolol has a greater effect compared with atenolol in patients with mild-to-moderate hypertension.     

Atenolol blunts blood pressure increase during dynamic resistance exercise in hypertensives

AIMS

This study was conducted to determine whether atenolol was able to decrease BP level and mitigate BP increase during dynamic resistance exercise performed at three different intensities in hypertensives.

METHODS

Ten essential hypertensives (systolic/diastolic BP between 140/90 and 160/105 mmHg) were blindly studied after 6 weeks of placebo and atenolol. In each phase, volunteers executed, in a random order, three protocols of knee-extension exercises to fatigue: (i) one set at 100% of 1 RM; (ii) three sets at 80% of 1 RM; and (iii) three sets at 40% of 1 RM. Intra-arterial radial blood pressure was measured throughout the protocols.

RESULTS

Atenolol decreased systolic BP maximum values achieved during the three exercise protocols (100% = 186 ± 4 vs. 215 ± 7, 80% = 224 ± 7 vs. 247 ± 9 and 40% = 223 ± 7 vs. 252 ± 16 mmHg, P < 0.05). Atenolol also mitigated an increase in systolic BP in the first set of exercises (100% =+38 ± 5 vs.+54 ± 9; 80% =+68 ± 11 vs. +84 ± 13 and 40% =+69 ± 7 vs.+84 ± 14, mmHg, P < 0.05). Atenolol decreased diastolic BP values and mitigated its increase during exercise performed at 100% of 1 RM (126 ± 6 vs. 145 ± 6 and +41 ± 6 vs.+52 ± 6, mmHg, P < 0.05), but not at the other exercise intensities.

CONCLUSIONS

Atenolol was effective in both reducing systolic BP maximum values and mitigating BP increase during resistance exercise performed at different intensities in hypertensive subjects.     

动态血压监测评价尼群洛尔片治疗原发性高血压的疗效

目的应用动态血压监测(ABPM)方法评价尼群洛尔片治疗原发性高血压的疗效。方法 22例原发性高血压患者经2周洗脱期,服用尼群洛尔片(尼群地平5 mg和阿替洛尔10 mg)2片/次,1次/d,4周末坐位舒张压(DBP)≥90 mmHg(1 mmHg=0.133 kPa)者加服1次。于洗脱期末及治疗8周末仍服药1次患者各行ABPM和实验室检查1次。结果ABPM显示8周末24 h平均血压、日间平均血压、夜间平均血压、白昼平均收缩压(SBP)负荷、夜间平均DBP负荷均比治疗前明显降低。降低SBP和DBP谷峰比分别为0.51和0.60;SBP和DBP的平滑指数分别为1.63和2.08,不良反应发生率低。结论尼群洛尔片每天服药1次治疗原发性高血压安全有效。     

Valsartan but not atenolol improves vascular pathology in diabetic Ren-2 rat retina

BACKGROUND: To determine whether angiotensin type 1 receptor blockade (AT1-RB) or antihypertensive therapy per se, attenuates acellular capillaries and proliferating endothelial cells in the retina of diabetic Ren-2 rats. METHODS: Eight-week-old hypertensive Ren-2 rats were made diabetic (streptozotocin, 55 mg/kg) or nondiabetic (0.1 mol/L citrate buffer) and studied for 20 weeks. Diabetic Ren-2 rats received by gavage the AT1-RB valsartan at 4, 10, or 40 mg/kg/d or the beta1-adrenergic receptor blocker atenolol at 30 mg/kg/d. Systolic blood pressure (BP) was measured every 4 weeks. Acellular capillaries (devoid of pericytes and endothelial cells) were counted on trypsin digests. Proliferating endothelial cells were evaluated using double immunolabeling for isolectin and proliferating cell nuclear antigen. RESULTS: Systolic BP was unchanged in control Ren-2 rats throughout the study (186.6 +/- 3.5 mm Hg, nondiabetic; 185.0 +/- 0.7 mm Hg, diabetic; week 20). In diabetic Ren-2 rats, 4 and 10 mg of valsartan and atenolol reduced systolic BP to a similar extent, and at 20 weeks were comparable to diabetic Sprague Dawley rats (123.0 +/- 1.4 mm Hg). In diabetic Ren-2 rats, 40 mg of valsartan reduced systolic BP (110.9 +/- 1.1 mm Hg, 20 weeks) below that of Sprague Dawley rats. Acellular capillaries and proliferating endothelial cells were increased by 3- and 1.6-fold, respectively, in diabetic Ren-2 controls and reduced with 4 and 10 mg of valsartan and further reduced with 40 mg of valsartan. Atenolol had no effect on retinal pathology in diabetic Ren-2 rats. CONCLUSIONS: Blockade of the renin-angiotensin system but not antihypertensive therapy with atenolol reduces vascular pathology in diabetic Ren-2 retina, suggesting that angiotensin II is a causative factor and therapeutic target in diabetic retinopathy.     

苯氧胺辅助治疗急性心肌梗塞性心力衰竭的研究

目的 探讨苯氧胺辅助治疗急性心肌梗塞性心力衰竭的疗效。方法 83例急性心肌梗塞性心力衰竭患随机分为两组，治疗组30例，两组均为治疗前后检测心率，血压，射血分数及心功能，所获数据经秩和检验和t检验。结果 治疗组显效40．00％，有效46．67％，有效率86．67％；对照组显效22．64％，有效35．85％，有效率58．49％，两组比较P＜0．01，差异有显性，两组治疗后均心率明显下降，射血分数提高，心功能改善，但治疗改善明显，P＜0．05。结论 应用苯氧胺治疗急性心肌梗塞性心力衰竭可减轻心室重构，改善心功能，是一种较好的药物。     

A comparison of Circulatory responsiveness following the sudden withdrawal from atenolol and propranolol

The sudden withdrawal of propranolol and atenolol was studiedin five normal volunteers. Exercise testing was performed duringthe withdrawal period and physiological responsiveness comparedto control responses. A significantly heightened reactivityof the blood pressure with early exercise was found after discontinuationof both drugs. A significant acceleration of the heart raleresponse with early exercise was seen only following propranololwithdrawal. When the combined effect (heart rate x systolicblood pressure) was analyzed, a significant increase in thedouble product achieved with low levels of exercise was observedfollowing the sudden withdrawal of only propranolol administration.     

阿替洛尔非pH依赖型缓释片的制备及处方优化

以羟丙甲纤维素为缓释材料,琥珀酸为pH缓冲剂制备非pH依赖型阿替洛尔缓释片.考察以不同用量的羟丙甲纤维素和琥珀酸配制成不同处方缓释片,测定各个处方在0.1mol/L盐酸和pH7.4磷酸盐缓冲液中的释放度,采用多指标同步优化筛选处方.结果表明,优化处方在不同pH介质中均有较好的缓释效果.     

血浆中阿替洛尔的HPLC测定

用Ｈｙｐｅｒｓｉｌ ＯＤＳ色谱柱,以磷酸二氢钾－乙腈为流动２相,采用反相高效液相色谱法测定血浆中阿替洛尔浓度。方法回收率高,结果准确,重现性好。