Hemodynamic characterization of left ventricular function in experimental coxsackieviral myocarditis: effects of carvedilol and metoprolol

BACKGROUND: Carvedilol, a vasodilating nonselective beta-adrenoceptor antagonist, but not metoprolol, a selective beta1-adrenoceptor antagonist, has been shown to increase the production of cardiac antiinflammatory cytokines in experimental myocarditis. However, the hemodynamic consequences of these differences had not been investigated until today. Therefore, we determined the effects of carvedilol and metoprolol on left ventricular function in a murine model of coxsackievirus B3 (CVB3)-induced myocarditis. METHODS: BALB/c mice were inoculated with the coxsackie-B3 virus. Four and 10 days after infection, left ventricular function was investigated using a conductance micromanometer system. Additional groups were treated starting 24 h after infection using equipotent doses of carvedilol and metoprolol and studied on day 10. RESULTS: On day 4, infected mice manifested increased afterload-enhanced contractility and abnormal diastolic function. On day 10, contractile function of untreated mice was impaired. Carvedilol significantly improved cardiac index and most systolic indices, whereas metoprolol was substantially less effective. Diastolic dysfunction was not influenced by either of the beta-adrenoceptor antagonists. CONCLUSIONS: These hemodynamic data indicate that not only beta1-adrenoceptor blockade but also pleiotropic effects are involved in the cardioprotective effects of carvedilol on the pathophysiology of acute viral myocarditis.     

Different intrinsic activities of bucindolol, carvedilol and metoprolol in human failing myocardium

1. Clinical studies have shown different effects of beta-blockers on the beta-adrenergic system, tolerability and outcome in patients with heart failure. 2. The study examines beta-adrenoceptor-G-protein coupling and intrinsic activity of bucindolol, carvedilol and metoprolol in human ventricular myocardium. 3. Radioligand binding studies ([(125)I]-Iodocyanopindolol) were performed in membrane preparations of human failing and nonfailing myocardium. Functional experiments were carried out in isolated muscle preparations of human left ventricular myocardium from failing hearts. 4. Bucindolol and carvedilol bound non-selectively to beta(1)- and beta(2)-adrenoceptors and exerted guanine nucleotide modulatable binding. Metoprolol was 35-fold beta(1)-selective and lacked guanine nucleotide modulatable binding. 5. All beta-blockers antagonized isoprenaline-induced enhancement of contractility. 6. In preparations in which the coupling of the stimulatory G-protein to adenylate cyclase was facilitated by forskolin, bucindolol increased force of contraction in three and decreased it in five experiments. Carvedilol increased force in one and decreased it in six experiments. Metoprolol decreased force in all experiments by 89. 4+/-2.2% (P<0.01 metoprolol vs carvedilol and bucindolol). The negative inotropic effect of metoprolol was antagonized by bucindolol. 7. It is concluded that differences in intrinsic activity can be detected in human myocardium and have an impact on cardiac contractility. In human ventricular myocardium, bucindolol displays substantially higher intrinsic activity than metoprolol and carvedilol. Bucindolol can behave as partial agonist or partial inverse agonist depending on the examined tissue. 8. Differences in intrinsic activity may contribute to differences in beta-adrenoceptor regulation and possibly to differences in tolerability and outcomes of patients with heart failure.     

Has COMET solved the controversy as to whether carvedilol is better than metoprolol in heart failure?

Carvedilol and metoprolol are beta(1)-adrenoceptor antagonists that decrease mortality in heart failure. It is not clear whether the ancillary properties, which carvedilol has but metoprolol does not have, contribute to the beneficial effect. The Carvedilol Or Metoprolol European Trial (COMET) compared metoprolol tartrate (mean daily dose 85 mg) and carvedilol (41.8 mg) in patients with heart failure. All-cause mortality was less in the carvedilol than the metoprolol group, indicating that at these doses, carvedilol has a mortality benefit over metoprolol. However, the beta(1)-adrenoceptor blocking activity of metoprolol tartrate (assessed by a decrease in heart rate) was slightly less than with carvedilol in COMET and less than that observed in previous mortality studies with metoprolol, suggesting that the use of metoprolol tartrate was not optimal in COMET.     

卡维地洛与琥珀酸美托洛尔治疗慢性收缩性心力衰竭的临床观察

目的： 分析卡维地洛与琥珀酸美托洛尔治疗慢性收缩性心力衰竭的临床疗效。方法： 选取于2009年1月-2011年1月在某院心内科接受治疗的慢性收缩性心力衰竭患者,随机分为A组和B组,其中A组应用卡维地洛进行治疗,B组应用琥珀酸美托洛尔进行治疗。待治疗24个月后随访两组患者的临床治疗效果、综合超声心动图主要指标、NT-proBNP的差异。结果： 共纳入267例收缩性心力衰竭患者,分析结果显示A组和B组治疗后左室射血分数、左室舒张末期内径及NT-proBNP明显改善,具有统计学意义（P<0.01）;与B组相比,A组对左心室射血分数的改善更加显著（P<0.05）,而对左室舒张末期内径和NT-proBNP的改善两组无统计学差异（P>0.05）。结论： 卡维地洛和琥珀酸美托洛尔均可明显改善慢性收缩性心力衰竭患者的心功能指标;与琥珀酸美托洛尔相比,卡维地洛能更显著提高慢性收缩性心力衰竭患者的左室射血分数。     

Beta-adrenoceptor genotype influences the response to carvedilol in patients with congestive heart failure

Although the widespread introduction of beta-adrenoceptor antagonists into the management of congestive heart failure (CHF) has led to significant improvements in morbidity and mortality, it is also apparent that clinical responses to this therapy vary substantially. With the recognition that functionally significant genetic polymorphisms of the beta2-adrenoceptor exist with clinically relevant allelic frequency, we hypothesized that beta2-adrenoceptor genotype may affect the response to carvedilol. The clinical response, influence on left ventricular function and beta2-adrenoceptor (beta2AR) genotype was determined in 80 patients treated with carvedilol. A clinically significant improvement in left ventricular function (good responder) was defined as an absolute improvement of 10% in the left ventricular ejection fraction or 5% in the fractional shortening. Consistent with studies performed in vitro on the influence of beta2AR genotype and receptor desensitization, subjects who were homozygous for the allele encoding the Gln27 polymorphism displayed a significantly lower proportion of good responders than patients who were homozygous or heterozygous for the Glu27 polymorphism (26% versus 63%, P=0.003). These data demonstrate a significant influence of beta2AR genotype in the response to carvedilol in CHF patients. Accordingly, determination of beta2AR status may be of value in the tailoring of individual therapy in patients with CHF.     

卡维地洛在慢性心力衰竭中的对照研究

目的：探讨卡维地洛在慢性心力衰竭中的应用，并与美托洛尔进行对照。方法：202例慢性心力衰竭患者随机分成2组，分别在常规治疗的基础上合用卡维地洛或美托洛尔治疗13周，观察慢性心力衰竭的改善情况。结果：卡维地洛治疗102例，心功能改善总有效率为89．2％，美托洛尔治疗组100例，心功能改善总有效率77％。结论：卡维地洛在慢性心衰中，对心功能的改善及左室舒张功能的好转优于美托洛尔。     

Antioxidant properties of carvedilol and metoprolol in heart failure: a double-blind randomized controlled trial

Animal and human studies have shown that carvedilol has significant antioxidant properties compared with other beta-blockers. The objective of this study was to determine if these antioxidant effects are detectable in patients with heart failure and to compare carvedilol with the selective beta-blocker metoprolol. Twenty-four patients with chronic heart failure were randomly assigned to receive either carvedilol or metoprolol in a double-blind control trial for 12 weeks in a University teaching hospital clinic. Blood pressure, heart rate, exercise tolerance, left ventricular ejection fraction, plasma total antioxidant status, erythrocyte superoxide dismutase, and glutathione peroxidase activities were determined at baseline and every 4 weeks up to 12 weeks. The results showed that erythrocyte superoxide dismutase and glutathione peroxidase were significantly reduced in carvedilol treated patients after 12 weeks of therapy, whereas metoprolol had no significant effect, although the clinical improvement over the short-term was similar with both drugs. Thus carvedilol, in addition to improving symptoms in heart failure, also possesses significant antioxidant properties. Whether this additional action influences long-term outcome is at present unknown.     

Differential effects of carvedilol on norepinephrine release in normoxic and ischemic heart

Carvedilol is a beta-adrenoceptor antagonist with multiple actions, which may contribute to superior cardioprotection in heart failure and myocardial infarction. We hypothesized that carvedilol may modulate presynaptic norepinephrine release in the heart. Therefore, we compared the effects of carvedilol (racemate and both enantiomers) and beta1-selective as well as nonselective beta-adrenoceptor blockers on norepinephrine release in isolated perfused rat hearts under normoxic and brief ischemic conditions. Exocytotic release of endogenous norepinephrine was induced by paired electric field stimulations to compare the release before (S1) and after (S2) beta-adrenoceptor blocker application. Metoprolol, bisoprolol, and pindolol (0.1-10 microM) had essentially no effect on exocytotic norepinephrine release under normoxic and ischemic conditions. In contrast, carvedilol exerted a biphasic concentration-response curve (increase followed by suppression) on norepinephrine release. The increase in norepinephrine release was more pronounced with R-carvedilol than with S-carvedilol, indicating an effect independent from beta-receptor antagonism. During ischemia, the facilitatory effect of carvedilol on norepinephrine release was lost, resulting in a concentration-dependent suppression of the release. These results indicate that carvedilol in contrast to classic beta1-selective and -nonselective beta-adrenoceptor blockers has pronounced effects on cardiac norepinephrine release with a remarkable difference between normoxic and ischemic conditions. Whereas a facilitation of norepinephrine release prevailed in normoxia, we observed a suppression of the release in ischemia. It remains to be established whether this unique action of carvedilol on cardiac sympathetic neurotransmission is of clinical relevance.     

卡维地洛治疗慢性心力衰竭的临床疗效观察

目的研究卡维地洛治疗慢性心力衰竭(CHF)患者的临床疗效及耐受性,为临床合理用药提供依据。方法108例CHF患者随机分为卡维地洛组、美托洛尔组及对照组,每组36例,所有患者治疗心力衰竭基础药物(洋地黄、利尿剂、血管紧张素转换酶抑制剂)不变,而卡维地洛组、美托洛尔组分别加用卡维地洛及美托洛尔。于治疗前及连续治疗6月后进行心功能(NY-HA)分级评估,测量心率、血压及心电图、超声心动图检测,观察LVEDD、LVESD及LVEF变化。结果2例因用药后病情恶化而退出,106例完成全程治疗及随访,结果显示,与治疗前比较,卡维地洛组及美托洛尔组均可显著改善心功能分级、LVEF,并降低血压及心率,(分别为P<0.05、P<0.01)。而对照组患者治疗前后心功能分级、LVEF、血压及心率的变化均无显著差异。卡维地洛组3例发生低血压,美托洛尔组发生低血压及心动过缓各1例,无死亡患者。对照组再次入院人数(17例)较卡维地洛组(2例)及美托洛尔组(4例)明显增加(P<0.01)。结论在心力衰竭常规药物基础上加用卡维地洛,可以明显改善心功能,降低再次入院率。     

Reduction by beta-adrenoceptor blockade of hypoxia-induced right heart hypertrophy in the rat.

1. The study was undertaken to assess the role of beta-adrenoceptors in the induction of compensatory cardiac hypertrophy in an in vivo model. 2. In the rat, exposure to severe hypoxia (6% inspired oxygen for 8 h day) caused a 51% increase in right heart weight and a 75% increase in haematocrit. 3. The hypoxia-induced right ventricular hypertrophic response was reduced by 65% by oral treatment with a high dose of the non-selective beta-adrenoceptor antagonist, propranolol (80 mg kg-1 body weight); the drug treatment caused only a minor reduction (6%) in secondary polycythaemia. 4. With a less severe degree of hypoxia (7% inspired oxygen) there was only minimal secondary polycythaemia (+15%), and a lesser degree of compensatory right ventricular hypertrophy in untreated rats (+33%). 5. Treatment with the beta 1-adrenoceptor antagonist, atenolol, in a dose of 80 mg kg-1 body weight abolished right ventricular hypertrophy in response to 7% inspired oxygen, without affecting haematocrit and caused a small reduction in the ratio of heart weight to body weight in normoxic rats. 6. The results show that the effect of propranolol on hypoxic right ventricular hypertrophy is not secondary to any effect on secondary polycythaemia as has previously been suggested and that a marked reduction of compensatory cardiac hypertrophy can be obtained by a beta 1-selective adrenoceptor antagonist. Thus these findings support the view that noradrenaline released from cardiac sympathetic nerve terminals exerts a trophic effect on myocardial cells and demonstrates that in vivo, this trophic effect can be reduced by beta 1-adrenoceptor blockade.     

通心络胶囊联合卡维地洛治疗慢性心力衰竭临床分析

目的 观察通心络腔囊联合卡维地洛治疗慢性心力衰竭的临床疗效和安全性.方法 选择慢性心力衰竭患者60例,随机分为对照组和观察组各30例,对照组常规给予强心甙、利尿剂、血管扩张剂和血管紧张素转换酶抑制剂等治疗.观察组在对照组治疗基础上应用通心络胶囊每次4粒(每粒0.26 g),每日3次;同时联合卡维地洛5～20mg口服,每日2次;两组疗程均为8周.结果 观察组心功能改善的总有效率为90.0％,高于对照组的70.0％,两组比较差异有统计学意义(P＜0.05).治疗后观察组心排出量(CO)、每搏输出量(SV)、左心室舒张末期内径(LVDd)、左心室射血分数(LVEF)均有显著改善(P＜0.05);而对照组只有LVEF明显改善(P＜0.05),且观察组LVEF改善优于对照组(P＜0.05).结论 应用通心络胶囊联合卡维地洛治疗慢性心力衰竭具有明显逆转左心室肥厚和改善患者的左心收缩功能.可作为治疗慢性心力衰竭的一线用药.     

Carvedilol in the treatment of chronic heart failure

Along with the angiotensin-converting enzyme inhibitors (ACEIs), the beta-adrenergic receptor blockers have gradually emerged to be standard in the therapy of heart failure. Individual beta-blockers that have been shown to reduce all-cause mortality in patients with heart failure include bisoprolol, metoprolol and carvedilol. Carvedilol distinguishes from the other beta-blockers as being a non-selective beta(1)- and beta(2)-receptor blocker with (1)-receptor blockade effect and anti-oxidant properties. The drug does not have sympathomimetic activity and has vasodilatory effects attributable to its (1)-receptor blockade property. Experimental and clinical studies have confirmed carvedilol's vasodilator, anti-oxidant and anti-apoptotic properties, which may contribute to its effect in reversing cardiac remodelling in animal models and patients with heart failure. These pharmacological properties render carvedilol a potentially useful agent in the treatment of patients with heart failure. Early studies of carvedilol in heart failure have reported beneficial haemodynamic effects but variable effects on exercise tolerance and clinical well being. The large-scale US Carvedilol Heart Failure Program and the Australian/New Zealand Heart Failure Collaborative Research Group reported beneficial effects of carvedilol on mortality, morbidity and clinical well being in patients with mild-to-moderate heart failure. The recently reported but yet unpublished preliminary results of the COPERNICUS study suggest that carvedilol improves mortality and morbidity in patients with advanced heart failure and severe symptoms. At this time, it is unclear whether the ancillary pharmacological properties of carvedilol can be translated to more superior clinical benefit compared to the other beta-blockers. Preliminary studies examining surrogate end points suggest that carvedilol may improve left ventricular ejection fraction (LVEF) more than metoprolol. More conclusive information regarding their relative effects of clinical outcomes will await the completion of the COMET study, which compares the effect of metoprolol and carvedilol on mortality and morbidity, expected at the end of the year 2002.     

The mechanism of carvedilol in experimental viral myocarditis

Carvedilol is a nonselective β-blocker with α1-adrenergic blocking and antioxidant properties. A number of preclinical experiments and clinical trials have demonstrated that carvedilol provides prominent benefit in heart failure. However, less research has been done in the area of animal models of viral myocarditis. This paper reviews the use of carvedilol in animal models of viral myocarditis. The experimental evidence strongly suggests that carvedilol, but not metoprolol (a selective β1-adrenergic blocking agent), protects against viral myocarditis and the superior cardioprotection effect of carvedilol to metoprolol may be due to its upregulating the production of antiinflammatory cytokines, downregulating the production of proinflammatory cytokines, antioxidative effects, the suppression of matrix metalloproteinases production, and positive hemodynamic effects.     

Improvement of cardiovascular effects of metoprolol by replacement of common salt with a potassium- and magnesium-enriched salt alternative.

1. The influence of sodium chloride (NaCl)-enrichment of the diet (6% of the dry weight) and that of a novel sodium-reduced, potassium-, magnesium-, and L-lysine-enriched salt alternative on the cardiovascular effects of the beta 1-adrenoceptor blocking drug, metoprolol, was studied in stroke-prone spontaneously hypertensive rats. 2. Increased dietary sodium chloride intake produced a marked rise in blood pressure and induced left ventricular and renal hypertrophy. By contrast, the salt alternative did not increase blood pressure and caused remarkably less cardiac and renal hypertrophy than did sodium chloride. 3. Metoprolol treatment at a daily dose of 250 mg kg-1 lowered blood pressure and decreased left ventricular hypertrophy index during the control diet. Sodium chloride-enrichment blocked the antihypertensive effect of metoprolol, while a partial protective effect on left ventricular and renal hypertrophy persisted. In the presence of the salt alternative-enrichment both at the level of 6% and 10.5% (corresponding to a NaCl level of 6%), metoprolol was fully able to exert its beneficial cardiovascular and renal effects. 4. Both salt supplementations, irrespective of metoprolol treatment, induced a 3 to 4 fold increase in the urinary excretion of calcium. There was a linear correlation between the urinary excretions of sodium and calcium. The urinary excretion of magnesium rose by 90% and that of potassium by 110% in the salt alternative group. 6. Our findings suggest that replacement of common salt by a potassium-, and magnesium-enriched salt alternative in the diet produces beneficial cardiovascular effects and improves the antihypertensive efficacy of metoprolol in stroke-prone spontaneously hypertensive rats.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hemodynamic effects at rest and during exercise of combined alpha/beta-receptor blockade and of beta-receptor blockade alone in patients with ischemic heart disease

The acute hemodynamic responses to beta-adrenoceptor blockade with the beta 1-selective antagonist metoprolol, and to combined alpha/beta-receptor blockade with labetalol, were compared intraindividually in a randomized single-blind, cross-over study. Fourteen patients with proved ischemic heart disease, aged 52-64 years, were studied at rest (supine) and during ischemia-inducing exercise (in the seated posture) using invasive percutaneous techniques. Metoprolol reduced heart rates and cardiac output greatly (p less than 0.001) and systemic arterial pressures slightly (p less than 0.001) under all conditions. Left ventricular filling pressures increased. Labetalol induced a slight decrease in heart rates during exercise, while cardiac output was unchanged. Systemic arterial pressures and vascular resistances, pressures and resistances in the pulmonary circulation, and left ventricular filling pressures were distinctly lower. During ischemia-inducing exercise, the differences between the effects of labetalol and metoprolol on heart rate, cardiac output, systemic vascular resistance, and left ventricular filling pressures were highly significant. The effects on the rate X pressure product and on angina were similar. It is concluded that combined alpha/beta-blockade with labetalol offsets or attenuates the potential adverse hemodynamic effects of beta-receptor blockade alone without loss of symptomatic efficacy.     

卡维地洛抗实验性心律失常作用

目的　评价卡维地洛（ＣＶＤ）抗实验性心律失常作用,并与β受体阻断剂普萘洛尔（ＰＲＯ） 进行比较。方法　采用氯仿致小鼠室颤（ＶＦ） , 哇巴因、乌头碱致豚鼠、大鼠心律失常,肾上腺素致豚鼠心律失常, 以及结扎大鼠冠状动脉诱发心律失常等５ 种模型。结果　与溶媒对照组相比, ＣＶＤ１ ｍｇ·ｋｇ－１ 显著降低氯仿诱发的小鼠ＶＦ 发生率〔１８－７５ ％（３／１６） ｖｓ８１－２５％ （１３／１６）,Ｐ＜ ０－０１〕,此作用与ＰＲＯ 相似。１ ｍｇ·ｋｇ－１ ＣＶＤ 和ＰＲＯ 均显著提高致室早（ＶＥ） , 室速（ＶＴ）, ＶＦ, 心搏停止（ＣＡ） 所需哇巴因和乌头碱用量（ Ｐ＜０－０１ ｖｓ 溶剂对照组） ;ＣＶＤ 对抗哇巴因的致心律失常作用较等剂量ＰＲＯ 显著（ Ｐ＜ ０－０１ ,ＣＶＤ ｖｓ ＰＲＯ）。ＣＶＤ 剂量依赖性地显著缩短ｉｖ 肾上腺素４０ μｇ·ｋｇ－ １ 所致心律失常持续时间,有效减少结扎冠脉诱发的缺血性心律失常ＶＴ,ＶＦ,ＣＡ 的发生率并缩短ＶＴ 的持续时间。结论　ＣＶＤ 具有抗多种实验性心律失常作用,该作用在等剂量时至少与ＰＲＯ 相近,或强于ＰＲＯ。ＣＶＤ的这种作用最终将有益于接受其治疗的原发性高血压、冠心病、充血性心力衰竭患者     

Oxygen radical system in chronic infarcted rat heart: the effect of combined beta blockade and ACE inhibition

In vitro experiments suggest that beta blockade and angiotensin-converting enzyme (ACE) inhibition may protect the failing heart by reduction of myocardial oxidative stress. To test this hypothesis in an in vivo model, the beta blocker metoprolol (350 mg) and the ACE inhibitor ramipril (1 mg) were given either alone or in combination to rats (per kilogram body weight per day) for 6 weeks after myocardial infarction. Left ventricular end-diastolic pressure (LVEDP), contractile function of papillary muscles, enzymatic antioxidative defense (indicated by the activities of the superoxide dismutase isoenzymes and glutathione peroxidase), and the extent of lipid peroxidation were studied. Placebo-treated rats showed cardiac hypertrophy, increased LVEDP, lower rates of contraction and relaxation, as well as a deficit in the myocardial antioxidative defense associated with increased lipid peroxide levels, when compared with sham-operated animals. Combined beta blockade and ACE inhibition improved the antioxidative defense, reduced hypertrophy and LVEDP, and enhanced rates of contraction. Thus prolonged beta blockade and ACE inhibition after infarction may decrease myocardial oxidative stress and thereby could be beneficial in heart failure.     

卡维地洛与美托洛尔治疗慢性充血性心力衰竭的作用比较

目的：比较分析卡维地洛与美托洛尔在治疗慢性充血性心力衰竭过程中的安全性以及临床治疗效果。方法选取2012年1月至2013年10月该院收治的慢性充血性心力衰竭患者86例,随机分为两组,各43例。观察组在常规治疗基础上给予卡维地洛治疗,对照组在常规治疗基础上给予美托洛尔治疗,对比分析两组治疗前后的心率、血压、左心室射血分数（LVEF）、左心室舒张末期内径（LVEDD）以及不良反应,判定两组的临床疗效。结果与治疗前比较,两组患者心率、血压、LVEDD、LVEF以及不良反应在治疗后均得以改善,差异有统计学意义（P〈0.05）。观察组患者治疗后的各项指标略优于对照组患者,且LVEF组间比较,差异有统计学意义（P〈0.05）。观察组和对照组治疗总有效率分别为93.0%和81.4%,差异有统计学意义（P〈0.05）。结论作为β受体阻滞剂,在改善慢性充血性心力衰竭患者心功能方面,卡维地洛优于美托洛尔,其疗效更好且不良反应较少。建议临床上优先选择卡维地洛作为治疗慢性充血性心力衰竭药物。     

Disparate effects of carvedilol versus metoprolol treatment of stroke-prone spontaneously hypertensive rats on endothelial function of resistance arteries

In human hypertension, blockade of beta-adrenoceptors does not improve resistance artery structure or endothelial dysfunction. We tested in hypertensive rats the hypothesis that carvedilol, a beta-blocker with antioxidant properties, would improve endothelial dysfunction, whereas the beta1-selective blocker, metoprolol, would not. Twenty-week-old SHRSP were treated orally for 10 weeks with carvedilol (50 mg/kg/day) or metoprolol (100 mg/kg/day), with or without hydralazine (25 mg/kg/day), the latter because neither beta-blocker was a very effective blood pressure-lowering agent in this model. Mesenteric arteries (lumen, <300 microm) were studied on a pressurized myograph. After 10 weeks, untreated SHRSP had a systolic blood pressure (mm Hg) of 239+/-3 that was unaffected by carvedilol or metoprolol treatment but decreased (p < 0.05) by hydralazine (187+/-4), carvedilol + hydralazine (221+/-3), and metoprolol + hydralazine (197+/-3). Carvedilol alone improved endothelium-dependent relaxation of resistance arteries, as elicited by the lowest concentration of acetylcholine studied (10(-7) M), whereas metoprolol had no effect. Hydralazine improved endothelial function as elicited by acetylcholine at a dose of 10(-6) M, also found under cotreatment with carvedilol but attenuated by cotreatment with metoprolol. Carvedilol or metoprolol alone had no significant effect on endothelium-independent relaxation produced by a nitric oxide donor (sodium nitroprusside). However, vessels from rats treated with carvedilol + hydralazine exhibited significantly greater relaxation than those from rats treated with metoprolol + hydralazine. These data suggest that carvedilol may have favorable effects on hypertension-related endothelial dysfunction not observed with metoprolol. Neither drug corrected small artery structure in SHRSP.     

卡维地洛及美托洛尔对慢性心力衰竭合并糖尿病患者的心功能及胰岛素抵抗的影响

目的 观察卡维地洛和美托洛尔对慢性心力衰竭（chronicheart failure,CHF）合并2型糖尿病（type2 diabetesmellitus,T2DM）患者的心功能及胰岛素抵抗的影响。方法CHF合并T2DM患者130例,根据常规治疗基础上加用卡维地洛与美托洛尔分为卡维地洛组（65例）和美托洛尔组（65例）。治疗12个月。结果（1）卡维地洛组及美托洛尔组心功能均较治疗前改善（P〈0．05）。LVEF均高于治疗前（P〈0．05）,舒张末期内径（LVEDd）、舒张末期容积指数（LVEDVI）、收缩末期容积指数（LVESVI）均低于治疗前（P〈0．05）。卡维地洛组疗效优于美托洛尔组（P〈0．05）。（2）卡维地洛组的胰岛素抵抗指数显著低于治疗前（P〈0．05）,而美托洛尔治疗前后无明显变化（P〉0．05）。结论卡维地洛和美托洛尔均能明显改善CHF合并T2DM患者的心功能,卡维地洛可改善胰岛素抵抗。