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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Carvedilol is a vasodilating beta-blocker and antioxidant approved for treatment of mild to moderate hypertension. angina, and congestive heart failure. Metoprolol is a beta1-selective adrenoceptor antagonist. When carvedilol and metoprolol were recently compared in clinical trials for heart failure, each showed beneficial beta-blocker effects such as improved symptoms, quality of life, exercise tolerance, and ejection fraction, with no between-group differences. When thiobarbituric acid reactive substance (TBARS) levels were measured in serum as an indirect marker of free radical activity, there were also no between-group differences. However, we had noted superior cardioprotection by carvedilol in comparison to metoprolol in ischemia and reperfusion models. We therefore examined antioxidant activity directly in cells and tissues. Here we show that in cultured rat cerebellar neurons, and in brain and heart membranes, carvedilol has far greater antioxidant activity than metoprolol, which is essentially inactive as an antioxidant in these model systems. The antioxidant activity of carvedilol could be explained by a greater degree of lipophilicity, as measured by its ClogP value of 3.841 as contrasted to a ClogP value of 1.346 for metoprolol. Alternatively, the molecular structure of carvedilol favors redox recycling, which the structure of metoprolol does not. Therefore, carvedilol could have additional pharmacologic effects that are favorable for long-term therapy.
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PMID:A comparison of carvedilol and metoprolol antioxidant activities in vitro. 1094 72

An open, comparative, cross-over 8-week trial of beta-blockers nebivolol and metoprolol in 30 patients with arterial hypertension (AH) studied the office, ambulatory blood pressure and heart rate levels, endothelium-dependent vasorelaxation, endothelial NOS and NO production. It was found that nebivolol activated the system eNOS-NO and improved vasomotor parameters of the endothelium. Metoprolol failed to activate enzyme eNOS activity and NO production to the same level and did not improve the endothelial vasomotor function. The antihypertensive activity of nebivolol was higher than that of metoprolol. Thus, nebivolol can be used in patients with AH and cardiovascular risk factors to correct endothelial dysfunction.
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PMID:[Pharmacological modulation of NO synthesis in patients with arterial hypertension and endothelial dysfunction]. 1293 13

Metoprolol is a selective beta(1)-adrenergic antagonist extensively used in major fields of cardiology since 1975. Metoprolol has proven its efficacy in reducing cardiovascular events and mortality in patients with hypertension and coronary heart disease in large clinical trials. Recently developed controlled release/extended release (CR/XL) formulation of metoprolol succinate was designed to provide relatively constant metoprolol plasma concentrations and beta(1)-blockade while retaining the convenience of once daily administration. The avoidance of high peak plasma concentrations with metoprolol succinate is associated with lesser degree of adverse effects and may improve patients compliance. This formulation of metoprolol has demonstrated efficacy in reducing cardiovascular events and mortality in patients with heart failure. More recently evidence for antiatherogenic activity of metoprolol succinate has been also obtained.
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PMID:[Metoprolol CR/XL: advanced formulation of a classical beta-blocker]. 1459 74

The aim of this work was to demonstrate an alteration of the anterior hypothalamic catecholaminergic system in aortic coarctated (ACo) rats by the perfusion of beta-adrenergic antagonist and the microinfusion of beta-adrenergic agonist. Wistar urethane-chloralose anesthetized rats were used. The carotid artery was cannulated for blood pressure recording and changes in blood pressure were measured. A concentric microdialysis probe was inserted in the anterior hypothalamus. Metoprolol (a beta(1)-adrenoceptor antagonist) perfusion (6 microg ml(-1)) reduced the mean arterial pressure (MAP) in the ACo rats but not in sham operated (SO) animals. The anterior hypothalamic infusion of non-specific beta-adrenergic agonist isoproterenol induced a dose-dependent decrease of blood pressure in both experimental groups, but the depressor response was significantly lower in ACo rats. The pretreatment with atenolol, a selective beta(1)-adrenoceptor antagonist, increased the depressor effect of isoproterenol in ACo rats, but not in SO rats. On the other hand, the hypotensive action of isoproterenol was significantly diminished after the administration of non-specific beta-adrenoceptor antagonist propranolol in SO and ACo rats. The anterior hypothalamic infusion of clenbuterol, a selective beta(2)-adrenergic agonist, induced a dose-dependent decrease of blood pressure in both experimental groups. The depressor response to clenbuterol (1 nmol) was significantly lower in ACo rats than in SO rats. In summary, this study provides the evidence that there is a beta(1)-adrenergic compromise in anaesthetized ACo rats and this compromise may be involved in the maintenance of hypertension. On the other hand, this study also suggests the existence of pressor beta(1)-adrenoceptors in the anterior hypothalamic area of ACo rats but not in SO rats. We also found a diminished depressor beta(2)-adrenergic activity in ACo rats.
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PMID:Anterior hypothalamic beta-adrenergic activity in the maintenance of hypertension in aortic coarctated rats. 1459 47

The present study addressed possible alterations in the pharmacodynamic and pharmacokinetic properties of the beta1-adrenoceptor antagonist metoprolol in experimental hypertension induced by abdominal aortic coarctation (ACo). Metoprolol's pharmacokinetics and its relationship with its in vivo chronotropic and blood pressure effect were studied using the microdialysis technique. A pharmacokinetic-pharmacodynamic model with a separate effect compartment was used to analyse the data. No differences were found in the calculated pharmacokinetic parameters between sham-operated (SO) and ACo rats. Bradycardia was observed after the i.v. injection of metoprolol (3 or 10 mg/kg) without differences between the experimental groups. The decrease of mean arterial pressure (DeltaMAP) induced by metoprolol was greater in ACo than in SO rats: SO: -14+/-2 mmHg, n=5; ACo: -26+/-4 mmHg, n=5, P<0.05. The dissociation constant (expressed as pKb) of metoprolol and its inverse agonistic activity were studied in isolated atria. The pKb of metoprolol was similar in both groups of animals (SO: 7.49+/-0.20; ACo: 7.19+/-0.23). The inverse agonistic activity of metoprolol on spontaneous beating of isolated atria was established by means of a concentration/response curve. There were no differences in maximum response (Emax; SO: -28+/-2.0%, n=5; ACo: -27+/-4%, n=5) or the concentration eliciting a half-maximal effect (pEC50) (SO: 4.9+/-0.2, n=5; ACo: 5.2+/-0.2, n=5) between the experimental groups. These results suggest that chronic ACo does not modify the beta-adrenoceptor affinity of metoprolol or its inverse agonistic activity. Moreover, there was no difference in the in vivo chronotropic effect between the experimental groups, indicating the absence of cardiac sympathetic over-activity in this model of hypertension. The pharmacokinetic results suggest that the metabolism of metoprolol is not affected in chronic ACo rats. In addition, the greater sensitivity to the depressor effect of metoprolol in ACo rats in the chronic hypertensive stage suggests a participation of the beta-adrenoceptors in the maintenance of hypertension.
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PMID:Pharmacokinetic-pharmacodynamic properties of metoprolol in chronic aortic coarctated rats. 1530 Mar 60

Metoprolol is a widely used beta1-selective beta-blocker in hypertension and tachycardia. The influence on vital signs at rest and during ergometry (exercise heart rate or blood pressure, effect areas above baseline) was investigated in a pilot study with 18 healthy volunteers (mean age 29.1 years) by means of multiple and pairwise correlation analysis. At rest, the difference between predose and day 5 values were not associated with anthropometric characteristics. During ergometry for weight and height significant negative correlations were found corresponding to marked beta-values in the multiple regression models. Therefore heart rate decreases less markedly in slim persons which should be taken into consideration in exercise tests during metoprolol intake.
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PMID:Relation between pharmacodynamic and anthropometric parameters during ergometry at rest and after repeated intake of metoprolol in healthy volunteers: results of a pilot study. 1533 32

Beta-blockers utilized in the Type 2 diabetic patient result in an even greater decrease in cardiac events than in the nondiabetic patient. Unfortunately, first-and second-generation beta-blockers are associated with the worsening of insulin resistance, deterioration of glycemic control, peripheral vasoconstriction, potentially worsening peripheral vascular disease, and more frequent and severe hypoglycemia. The third-generation beta-blockers have unique properties, including alpha1-blockade, and have been shown to lower insulin resistance, improve glycemic control, and vasodilate resistance arterioles. The Glycemic Effects in Diabetes Mellitus: Carvedilol-Metoprolol Comparison in Hypertensives (GEMINI) trial has been designed to compare a third-generation (carvedilol) with a second-generation beta-blocker (metoprolol) in a cohort of participants with hypertension and Type 2 diabetes. The primary outcome measure of the study is change in the HbA1c. The study is powered to detect a difference in HbA1c of 0.3 units (%) between the groups. Secondary endpoints include changes in insulin resistance, fasting glucose, and the lipid profile. Differences in the side-effect profile (cold extremities, fatigue, impotence, and hypoglycemia) will also be assessed. The GEMINI trial, therefore, is the first large randomized trial to assess whether utilizing a third-generation beta-blocker yields a favorable metabolic profile in the patient with Type 2 diabetes and hypertension.
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PMID:The rationale and design of the Glycemic Effects in Diabetes Mellitus Carvedilol-Metoprolol Comparison in Hypertensives (GEMINI) trial. 1574 36

Increases in the cardiovascular risk marker microalbuminuria are attenuated by blood pressure reduction using blockers of the renin-angiotensin system. Such changes in microalbuminuria have not been observed when beta-blockers are used. A prespecified secondary end point of the Glycemic Effects in Diabetes Mellitus Carvedilol-Metoprolol Comparison in Hypertensives (GEMINI) trial was to examine the effects of different beta-blockers on changes in albuminuria in the presence of renin-angiotensin system blockade. Participants with hypertension and type 2 diabetes were randomized to either metoprolol tartrate (n=737) or carvedilol (n=498) in blinded fashion after a washout period of all antihypertensive agents except for angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. Blinded medication was titrated to achieve target blood pressure, with a-5 month follow-up period. The current analysis examined microalbuminuria, using spot urine albumin:creatinine, in participants who had values at screening and trial end. A greater reduction in microalbuminuria was observed for those randomized to carvedilol (-16.2%Delta; 95% confidence interval, -25.3, -5.9; P=0.003). Of those with normoalbuminuria at baseline, fewer progressed to microalbuminuria on carvedilol versus metoprolol (20 of 302 [6.6%] versus 48 of 431 [11.1%], respectively; P=0.03). Microalbuminuria development was not related to differences in blood pressure or achievement of blood pressure goal (68% carvedilol versus 67%, metoprolol). Presence of metabolic syndrome at baseline was the only independent predictor of worsening albuminuria throughout the study (P=0.004). Beta-blockers have differential effects on microalbuminuria in the presence of renin-angiotensin system blockade. These differences cannot be explained by effects on blood pressure or alpha1-antagonism but may relate to antioxidant properties of carvedilol.
Hypertension 2005 Dec
PMID:Differential effects of beta-blockers on albuminuria in patients with type 2 diabetes. 1628 77

Although beta-adrenoceptor antagonists (beta-blockers) have effects on metabolism via their mechanism as blockers of adrenergic stimulation, most interest in the metabolic effects of beta-blockers is caused by their effect on glucose metabolism. Strict metabolic control and management of cardiovascular risk factors in patients with diabetes mellitus has proven to be of great importance in the improvement of prognosis. Beta-blockers are necessary tools for the treatment of heart failure and hypertension. The use of beta-blockers in patients with diabetes mellitus has been controversial because of fear of deterioration of metabolic control of glucose and lipids and blunting of the symptoms of hypoglycemia. Currently, it appears that there is a beneficial metabolic effect with the third-generation beta-blocker carvedilol. Comparisons have been made between the second-generation beta-blocker metoprolol and carvedilol, with a clear advantage for carvedilol in terms of metabolic control. In the GEMINI (Glycemic Effects in Diabetes Mellitus: Carvedilol-Metoprolol Comparison in Hypertensives) trial, a decrease of 9.1% (p = 0.004) in insulin resistance, compared with baseline values, was seen in patients treated with carvedilol, whereas no significant difference was seen in the group of patients treated with metoprolol. Additionally, an increase in glycosylated hemoglobin of 0.15% from baseline was seen in the metoprolol group (p < 0.001) compared with no significant change in the carvedilol group. These findings indicate that, as carvedilol exerts favorable effects on glucose metabolism compared with metoprolol, patients with diabetes mellitus could benefit from treatment with carvedilol rather than metoprolol. The mechanisms behind these findings are not yet fully understood. Several mechanisms have been suggested, and special interest has been paid to the investigation of the potential beneficial role of the beta2- and alpha1-adrenoceptor-blocking effects of carvedilol, along with its known antioxidant properties.
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PMID:Metabolic effects of beta-adrenoceptor antagonists with special emphasis on carvedilol. 1691 22

Recently, various clinical studies have indicated that lipophilic beta-blockers reduce the coronary mortality in diabetic patients; however, systematic studies have not been reported. The objective of the present investigation was to compare the effects of chronic treatment with metoprolol and atenolol on cardiovascular complications in streptozotocin (STZ)-induced diabetic rats. Injection of STZ produced hyperglycemia, hypoinsulinemia, hyperlipidemia, increased blood pressure, cardiac hypertrophy, reduction in heart rate, and structural alterations in cardiac tissues. Metoprolol and atenolol effectively prevented the development of hypertension in diabetic rats. Metoprolol treatment produced a slight but significant reduction in serum glucose levels with elevation in serum insulin levels, while atenolol produced a slight increase in glucose levels but no effect on insulin levels. Moreover, neither metoprolol nor atenolol treatment reduced the elevated cholesterol levels in diabetic rats. Metoprolol treatment significantly prevented STZ-induced increase in triglyceride levels, but atenolol failed to produce this effect. Metoprolol exhibited a minimal improvement in STZ-induced bradycardia, whereas atenolol produced a further reduction in heart rate. Histological examination showed metoprolol treatment also prevented STZ-induced hypertrophy and some of the alterations in cardiomyocytes. In conclusion, our data suggest that metoprolol has some beneficial effects over atenolol with respect to cardiovascular complications associated with diabetes mellitus.
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PMID:Comparative evaluation of atenolol and metoprolol on cardiovascular complications associated with streptozotocin-induced diabetic rats. 1790 94


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