Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Oxidative stress has been suggested to be an etiological factor in cerebro- and cardiovascular disorders. We examined antioxidant activities of carvedilol, a beta- and alpha-adrenoreceptor blocker. Carvedilol suppressed lipid auto-oxidation and protein carbonyl formation in brain homogenate in a dose-dependent manner. Carvedilol also suppressed superoxide generation of human neutrophils. These properties of carvedilol should be suitable for treating hypertension resulting in cerebro- and cardiovascular diseases.
 ...
PMID:Antioxidant properties of carvedilol: inhibition of lipid peroxidation, protein oxidation and superoxide generation. 1457 94

Cardiac mitochondria may become dysfunctional during ischaemia, thus compromising cardiomyocyte function. Carvedilol is an alpha(1)/beta-adrenoceptor antagonist with antioxidant, neuroprotective, cardioprotective and vascularprotective properties, and is used to treat hypertension, myocardial ischaemia and congestive heart failure. However, its impact on mitochondrial function during acute prolonged ischaemia is unknown. We aimed to study the effect of carvedilol on cardiac mitochondrial function during acute ischaemia, using Wistar rat hearts perfused with a Langendorff system, and then submitted to ischaemia in the presence and absence of carvedilol. We determined the electrical potential of the mitochondrial membrane, O(2) consumption by the respiratory chain, energy charge and the activity of the mitochondrial respiratory chain complexes. In our model, carvedilol had a preferential action on phosphorylation, increasing the mitochondrial energy charge (0.76+/-0.03 vs. 0.65+/-0.01 arbitrary units; P<0.05) and decreasing the phosphorylation lag phase (28.64+/-4.23 vs. 62.4+/-11.63 s; P<0.05) during ischaemia. The larger amount of energy available allowed the preservation of the electrical potential (201.2+/-2.45 vs. 186.66+/-3.36 mV;P<0.05), thus improving mitochondrial function during acute prolonged ischaemia.
 ...
PMID:Carvedilol improves energy production during acute global myocardial ischaemia. 1466 29

Carvedilol is a multiple-action drug with alpha(1)- and beta-adrenergic receptor antagonistic, calcium channel blocker and antioxidant activities especially useful in the treatment of hypertension. The antioxidant activity of the drug depends on the carbazole moiety, which is unique to carvedilol and is also present in some of the metabolites lacking either the alpha(1)- or beta-adrenergic receptor blocking activity. These antioxidant properties account for the exceptional ability of carvedilol to reduce cardiac necrosis in animal models of myocardial infarction, as well as its neuroprotective activities in in vivo and in vitro models of brain ischemia. A further property of carvedilol is its ability to inhibit vascular smooth muscle cell migration and proliferation, and neointima formation, after vascular injuries. The identification of all these activities of carvedilol indicates that it is a singular multiple-action antihypertensive agent with potential for cardiovascular organ protection beyond the normalization of high blood pressure.
 ...
PMID:Carvedilol: an effective antihypertensive drug with antiischemic/antioxidant cardioprotective properties. 1474 60

Until recently elevated blood pressure was considered as a hemodynamic entity representing an increase in workload for the heart and the arterial tree. Control of hypertension meant hemodynamic unloading, through inhibition of vasoconstrictor pathways, principally renin-angiotensin system and sympathetic system. In recent years however a new pharmacological approach has evolved as a result of (i) the dissociation of endothelial dysfunction and vascular pathology from increased blood pressure; (ii) the recognition that endothelial dysfunction regards not only the vascular reactivity, but also promotes atherosclerosis and thrombosis; and (iii) an improved understanding of the complexity of local-tissue renin angiotensin system and of the vasodilatory and cytoprotective role of natriuretic peptides. This has led to a reconsideration of existing medicines in terms of specification on endothelial function, more rationalized application of drugs and search for new compounds targeting both vasodilatory and anti-proliferative pathways. Examples include beta1-adrenergic antagonists, such as Nebivolol and Carvedilol, and vasopeptidase inhibitors, such as Omapatrilat, that inhibit simultaneously the angiotensin converting enzyme and neutral endopeptidase. Furthermore the identification of genetic polymorphisms in the effectors involved in the pathophysiology of hypertension or in the response to anti-hypertensive drugs, such as the p22phox subunit of NADPH oxidase, alpha-adducin or adrenergic receptors, has promoted the prospective of both better understanding of hypertension and individualized strategies for its treatment.
 ...
PMID:The shift in the "paradigm" of the pharmacology of hypertension. 1496 15

Hypertension in spontaneously hypertensive rats (SHR) has been permanently abolished by aggressive treatment regimens targeted against the sympathetic nervous system and adrenal medulla, initiated during the pre-weaning period (guanethidine and nerve growth factor antiserum combined with either adrenal demedullation or prazosin treatment). To investigate the components of the sympatho-adrenal system involved, we treated pre-weaning SHR with the combined alpha(1)- and beta-adrenoceptor antagonist carvedilol (60 mg/kg/day s.c.; postnatal days 1-21). Carvedilol treatment significantly blocked adrenoceptors during the treatment period, delayed development (eye opening), reduced growth, and reduced arterial pressure and heart rate. However, there was only modest attenuation of the subsequent development of hypertension at 10 weeks of age (mean arterial pressure 129.5+/-1.8 versus 136.1+/-1.6 mm Hg in vehicle-treated littermates; P<0.05). Thus pre-weaning carvedilol treatment slightly but significantly attenuated the development of SHR hypertension at 10 weeks, suggesting that the profound antihypertensive effects of pre-weaning sympatho-adrenal ablation are attributable to factors other than alpha(1)- and beta-adrenoceptor-mediated effects of catecholamines during this period.
 ...
PMID:Pre-weaning carvedilol treatment in spontaneously hypertensive rats. 1497 7

In 1983, carvedilol [1-[carbazolyl-(4)-oxy]-3-[(2-methoxyphenoxyethyl)amino]-2-propanol] was designed and developed as a beta-adrenoceptor antagonist with vasodilating activity for efficacious and safe treatment of hypertension and coronary artery disease. Carvedilol belongs to the 'third generation' of beta-adrenoceptor antagonists and shows selectivity for the beta1- rather than beta2-adrenoceptor. Carvedilol is also an alpha1-blocking agents, with around 2- to 3-fold more selectivity for beta1- than alpha1-adrenoceptors. This degree of alpha1-blockade is responsible for the moderate vasodilator properties of carvedilol, being different from other beta-adrenoceptor antagonists. In addition, carvedilol is a potent antioxidant, with a 10-fold greater activity than vitamin E. Some carvedilol metabolites found in human plasma also exhibit antioxidative activity approximately 50- to 100-fold greater than carvedilol and other antioxidants. These unique properties of carvedilol, i.e. adrenergic (beta1, beta2 and alpha1) blockade and antioxidative activity, may be important in preventing progressive deterioration of left ventricular dysfunction and chronic heart failure. Recently, carvedilol has been demonstrated to reverse multidrug resistance (MDR) to anticancer drugs in tumor cells in vitro and its reversal effects were comparable with verapamil, which has been used in the first clinical trial for the reversal of MDR. This review introduces the reversal activity and usefulness against MDR, as well as an overview of the pharmacological and pharmacokinetic properties, of carvedilol.
 ...
PMID:Carvedilol: a new candidate for reversal of MDR1/P-glycoprotein-mediated multidrug resistance. 1505 33

Carvedilol is an adrenergic antagonist with nonselective beta- and a1-receptor blocking properties that has demonstrated significant clinical benefit in the management of patients with heart failure and in the post-myocardial infarction setting. It also possesses unique ancillary properties that may account for positive results in a number of clinical trials. It appears to offer particular advantages in the treatment of comorbid conditions, including coronary artery disease, stroke, hypertension, renal failure, diabetes, and atrial fibrillation, that can independently contribute to the progression of heart failure.
 ...
PMID:Carvedilol: beta-blockade and beyond. 1518 40

Experiments were performed to investigate the effects of long-term treatment with adrenergic receptor antagonist on electrical remodeling of the left ventricle with chronic pressure-overload. New Zealand rabbits underwent subtotal banding of superrenal abdominal aorta. At 10 weeks after surgery, echocardiography examination was performed, then action potential (AP), inward rectifier potassium current (I(Ki)), delayed rectifier potassium current (I(K)) and Na(+)/Ca(2+) exchanger current (I(Na(+)/Ca(2+))) were recorded in midmyocardial cells isolated from left ventricle of abdominal aorta banded group (banded group), abdominal aorta banding plus Carvedilol intervention group (Carvedilol group), and normal control group rabbits by using the whole-cell patch-clamp techniques. The results showed that left ventricular mass index in control, banded, and Carvedilol groups were 1.78+/-0.06 (n=7), 2.33+/-0.11 (n=7), and 1.87+/-0.08 (n=7), respectively (banded vs control and Carvedilol, P<0.01). At basic cycle length of 2 s, AP duration (measured at 90% repolarization, APD(90), ms) in control, banded, and Carvedilol groups were 522.0+/-19.5 (n=6), 664.7+/-46.2 (n=7), 567.8+/-14.3 (n=8) respectively (banded vs control, P<0.01; Carvedilol vs banded, P<0.05). At test potential of -100 mV, inward I(Ki) density (pA/pF) in control, banded, and Carvedilol groups were -11.8+/-0.50 (n=8), -8.07+/-0.28 (n=8), -10.69+/-0.35 (n=8) respectively (banded vs control and Carvedilol, P<0.01). At test potential of +50 mV, I(K) tail current density (pA/pF) in control, banded, and Carvedilol groups were 0.59+/-0.04 (n=8), 0.40+/-0.02 (n=9), 0.51+/-0.02 (n=8) respectively (banded vs control, P<0.01; Carvedilol vs banded, P<0.05). At test potential of +60 mV, outward I(Na(+)/Ca(2+)) density (pA/pF) in control, banded, and Carvedilol groups were 1.06+/-0.11 (n=8), 1.54+/-0.10 (n=9), 1.24+/-0.07 (n=8), respectively (banded vs control and Carvedilol, P<0.01). At test potential of -120 mV, inward I(Na(+)/Ca(2+)) density (pA/pF) in control, banded, and Carvedilol groups were -0.54+/-0.06 (n =8), -0.75+/-0.04 (n=9), -0.60+/-0.03 (n=8), respectively (banded vs control, P<0.01; Carvedilol vs banded, P<0.05). It is shown that long-term treatment with Carvedilol not only prevents development of cardiac hypertrophy, but also improves the electrophysiological alterations in rabbit hearts with chronic pressure-overload. This finding may add new electrophysiological evidence for the treatment of heart failure and hypertension with adrenergic receptor antagonist.
 ...
PMID:Adrenergic receptor antagonist prevents the left ventricle with chronic pressure-overload from electrical remodeling. 1532 84

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.
 ...
PMID:The rationale and design of the Glycemic Effects in Diabetes Mellitus Carvedilol-Metoprolol Comparison in Hypertensives (GEMINI) trial. 1574 36

The purpose of this pilot study was to test whether carvedilol has a protective effect against oxidative deoxyribonucleic acid (DNA) damage in human hypertension in vivo. Carvedilol's antioxidant effect has mostly focused on lipid or amino acid so far. However, there has been no data that carvedilol reduces DNA damage in human hypertension. Never-treated mild to moderate hypertension patients and age- and sex-matched control subjects volunteered for the study. The hypertension subjects were given 12.5 or 25 mg of carvedilol or hydrochlorothiazide orally for 2 months and controls were not given any. Fasting blood samples were collected before and after carvedilol. Plasma highly sensitive 8-hydroxy-2'-deoxyguanosine (hs8-OHdG) and high-sensitivity C-reactive protein (hsCRP) were checked with the samples. There were no statistical differences in clinical characteristics in 3 groups. The hs8-OHdG declined from 9.07+/-4.23 ng/mL to 5.74+/-3.89 ng/mL (P=0.002) after carvedilol. However, it did not show significant reduction after hydrochlorothiazide (9.01+/-3.89 versus 8.23+/-4.12 ng/mL; P=NS). In the control group, the hs8-OHdG concentration was 3.41+/-2.03 ng/mL and 3.01+/-2.65 ng/mL at baseline and 2 months later, respectively (P=NS). The baseline hs8-OHdG levels were higher in hypertension groups compared with control (P=0.000). The hsCRP had no significant difference before and after the tested drugs in 2 hypertension groups (group A: 0.21+/-0.51 versus 0.19+/-0.37 mg/dL; group B: 0.20+/-0.45 versus 0.18+/-0.42 mg/dL). In conclusion, DNA damage caused by reactive oxygen species occurs more in the hypertension patients than normals. Carvedilol significantly reduces DNA damage in the hypertension patients.
Hypertension 2005 May
PMID:Carvedilol reduces plasma 8-hydroxy-2'-deoxyguanosine in mild to moderate hypertension: a pilot study. 1583 35


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>