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

The effects of carvedilol, a novel cardiovascular agent, were evaluated in developing spontaneously hypertensive rats (SHR) for effects on hemodynamics, and the ability to effect the development of left ventricular, and vascular hypertrophy associated with chronic hypertension. Chronic oral administration of low dose carvedilol (20 mg/kg/day) was initiated when rats were 5 weeks of age, and experiments progressed until 14 weeks of age. Carvedilol-treated SHR had significantly reduced systolic blood pressures and heart rates throughout the duration of the experiment, and had significantly reduced ventricle/body weights by approximately 9.0%. Morphologic analysis of tertiary branches of the mesenteric artery revealed that carvedilol-treated SHR had significant reductions in medial cross-sectional area. Carvedilol produced concentration-dependent inhibition of basal [3H]thymidine incorporation in cultured SHR vascular smooth muscle cells, as well as by stimulation produced by PDGF (1 nM), EDGF (1 nM), thrombin (0.5 U/ml), or endothelin-1 (1 nM), indicating that carvedilol had direct anti-mitogenic activity. The present studies demonstrate that low dose carvedilol produced sustained reductions in blood pressure and heart rate in developing SHR that were accompanied by significant inhibition in the development of vascular and myocardial hypertrophy. The morphological changes induced by carvedilol may be mediated by a combination of hemodynamic effects, as well as by direct anti-mitogenic effects on vascular smooth muscle.
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PMID:Carvedilol, a novel cardiovascular agent, inhibits development of vascular and ventricular hypertrophy in spontaneously hypertensive rats. 819 8

Carvedilol is a cardiovascular drug currently used for the treatment of hypertension. Clinical studies have recently demonstrated efficacy in angina and congestive heart failure. Recently, carvedilol has been shown to attenuate oxygen free radical-initiated lipid peroxidation and to inhibit vascular smooth muscle mitogenesis induced by a wide variety of growth factors. These findings are of interest since smooth muscle proliferation and abnormal lipid metabolism are proposed to play an important role in the pathogenesis of atherosclerotic plaque formation and in development of stenotic lesions following vascular injury by balloon angioplasty and coronary artery bypass grafting. On the basis of these observations, the antiproliferative actions of carvedilol have been explored in detail. In human cultured pulmonary artery vascular smooth muscle cells, carvedilol (0.1-10 microM) produced a concentration-dependent inhibition of the mitogenesis stimulated by platelet-derived growth factor, epidermal growth factor, thrombin, and serum, with IC50 values ranging from 0.3 to 2.0 microM. Carvedilol also produced a concentration-dependent inhibition of vascular smooth muscle cell migration induced by platelet-derived growth factor, with an IC50 value of 3 microM. The extensive neointimal formation that occurs following balloon angioplasty of rat carotid arteries was markedly attenuated by carvedilol (1 mg/kg, i.p.; twice daily starting 3 days before angioplasty and continuing until 14 days after angioplasty). Quantitative image analysis demonstrated that carvedilol reduced the neointimal growth following angioplasty by 84% without altering either medial or adventitial cross-sectional areas. These observations indicate that carvedilol may also be effective in the treatment of pathological disorders principally associated with abnormal vascular smooth muscle growth, such as atherosclerosis and acute vascular wall injury induced by angioplasty or coronary artery bypass grafting.
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PMID:Carvedilol, a cardiovascular drug, prevents vascular smooth muscle cell proliferation, migration, and neointimal formation following vascular injury. 832 99

Carvedilol is a novel multiple-action cardiovascular drug that has recently been introduced to the market for the treatment of mild to moderate hypertension. Clinical studies have demonstrated that once daily therapy with carvedilol is efficacious and has a favourable side-effect profile. Clinical studies are in progress to establish the utility of carvedilol in angina and congestive heart failure. Carvedilol is a beta-adrenoceptor antagonist and a vasodilator, with the vasodilating activity resulting primarily from alpha 1-adrenoceptor blockade and possibly also from calcium channel blockade. The reduction in BP produced by carvedilol results from the vasodilating activity of the drug because peripheral vascular resistance is significantly reduced. The reduction in BP produced by carvedilol is not associated with reflex tachycardia owing to the beta-adrenoceptor blocking activity of the compound. Throughout its antihypertensive dose range, carvedilol has been a renal-sparing antihypertensive agent in animals and also in humans, inasmuch as renal blood flow, glomerular filtration rate and sodium excretion are all maintained. In preclinical experimental models of acute myocardial infarction, carvedilol has produced marked reductions in infarct size in the pig, rat and dog. The cardioprotection observed with carvedilol is greater than that provided by beta-adrenoceptor antagonists alone, suggesting that the additional activities of carvedilol may provide benefit in the setting of myocardial ischaemia.
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PMID:Preclinical and clinical pharmacology of carvedilol. 848 45

Carvedilol is a non-selective beta-adrenoceptor antagonist with vasodilating properties which has been shown to be effective in the management both of hypertension and of stable angina pectoris. In order to explore its wider efficacy in patients with manifest heart failure, a preliminary study was performed in patients with chronic stable angina pectoris accompanied by abnormal left ventricular wall motion, but without overt heart failure (mean ejection fraction < 40%). Six patients were given carvedilol 25 mg b.i.d. for 2 weeks followed by 50 mg b.i.d. for a further 2 weeks according to a single-blind placebo-controlled protocol. At the end of the 4 week period of treatment, in four patients left ventricular wall motion was improved, in two it was unchanged, and in none was there any deterioration; mean ejection fraction increased from 40 to 48%. These results prompted a further study in 17 patients with chronic ischaemic heart failure. The haemodynamic and clinical responses to intravenous carvedilol followed by the oral drug (50 mg b.i.d.) for 8 weeks were studied. There was an improvement in all haemodynamic variables, although postural hypotension necessitated withdrawing two patients, and clinical deterioration was evident in two others. The beneficial effects of carvedilol were considered to be related to the combined reduction in afterload and inhibition of neurohumeral activation. These results have been confirmed in placebo-controlled, double-blind studies.
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PMID:Vasodilating beta-blockers in heart failure. 852 82

Carvedilol is a vasodilating, beta-adrenoceptor antagonist currently marketed for the treatment of mild to moderate hypertension. Carvedilol acts to reduce total peripheral resistance by blocking peripheral vascular alpha 1-adrenoceptors, thereby producing systemic arterial vasodilation, while at the same time inhibiting reflex tachycardia through the blockade of myocardial beta-adrenoceptors. In addition to its established efficacy and safety as an antihypertensive agent, carvedilol has been shown to produce significant cardioprotection in experimental animal models of acute myocardial infarction, with the most dramatic effect being observed in the pig model of myocardial ischaemia and reperfusion, where the reduction in infarct size reached 91%. Recent pharmacological studies have revealed additional novel properties of carvedilol which may account for the marked protection produced by the drug in the ischaemic myocardium and which may also result in protection against other chronic pathological processes, such as atherosclerosis and acute vascular injuries. The latter arise from surgical procedures, such as percutaneous transluminal coronary angioplasty and coronary artery bypass grafting. Specifically, carvedilol, as well as some of its hydroxylated metabolites, are potent antioxidants. In physicochemical, biochemical and cellular assays, carvedilol and several of its metabolites prevent lipid peroxidation and the depletion of endogenous antioxidants, such as vitamin E and glutathione. Moreover, carvedilol and its metabolites prevent the oxidation of LDL to oxidized LDL, the latter being directly cytotoxic and known to activate monocytes/macrophages and to stimulate foam cell formation. In addition, carvedilol was found to inhibit both rat and human vascular smooth muscle cell proliferation and migration.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Carvedilol, a novel multiple action antihypertensive agent with antioxidant activity and the potential for myocardial and vascular protection. 852 83

Carvedilol is a vasodilating beta-blocker currently marketed for the treatment of mild to moderate hypertension and application is being filed to the FDA for treatment of congestive heart failure. Carvedilol reduces peripheral vascular resistance by blocking arterial alpha 1-adrenoceptors, thereby producing vasodilation, while preventing reflex tachycardia by blocking cardiac beta 1- and beta 2-adrenoceptors. In addition to the safety and efficacy of carvedilol as an antihypertensive agent, experimental studies indicate that carvedilol also provides significant cardioprotection in animal models of acute myocardial infarction as well as protection against the vascular remodelling that occurs following injury of the vasculature. Recent pharmacological studies have uncovered several novel properties of carvedilol which may function to protect the heart and vasculature from chronic pathological processes, such as ischaemia, atherosclerosis and the remodelling that occurs in the heart and blood vessels as a consequence of pressure overload, injury or shear stress. Specifically, carvedilol, likely as a result of the carbazol moiety, is a potent anti-oxidant. In physicochemical, biochemical and cellular assays carvedilol and several of its metabolites inhibit lipid peroxidation, scavenge oxygen free radicals, inhibit the formation of reactive oxygen radicals and prevent the depletion of endogenous antioxidants, such as vitamin E and glutathione. Moreover, carvedilol blocks the oxidation of low-density lipoproteins (LDL), and thereby prevents the formation of oxidized-LDL which is believed to stimulate foam cell formation and augment the development of atherosclerotic plaque. The ability of carvedilol to prevent the formation of oxidized LDL, in addition to the general anti-oxidant properties of the compound, results in the protection of the endothelium from oxygen free radical injury, and thereby prevents the subsequent events triggered by endothelial damage. Recently, carvedilol has also been shown to inhibit vascular smooth muscle cell proliferation and migration. Because carvedilol can inhibit vascular smooth muscle cell proliferation induced by a wide variety of mitogens (e.g. growth factors, angiotensin II, endothelin, thrombin), it is likely that the site of inhibition occurs at some point beyond the specific mitogen receptors, possibly at a distal common pathway that affects the smooth muscle cell cycle. These unique activities of carvedilol have also been confirmed in vivo in a rat model of neointimal formation following vascular injury by balloon angioplasty, where vascular smooth muscle cell migration and proliferation are the key processes involved in the formation of neointima leading to vascular stenosis. In this model, carvedilol suppressed neointimal growth to a remarkable extent ( > 85% inhibition of neointimal formation) at a dose that is similar to the antihypertensive dose used clinically in hypertensive patients. Taken together, these unique multiple actions of carvedilol provide not only for adequate control of elevated blood pressure, but may also provide for protection of the heart and vasculature from secondary damage due to hypertension itself, as well as from other causes, such as ischaemia, pressure overload, shear stress, vascular injury and atherosclerosis.
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PMID:Carvedilol, a novel vasodilating beta-blocker with the potential for cardiovascular organ protection. 873 68

The effects of carvedilol, a novel vasodilating beta-blocker and antioxidant, and propranolol on survival, neurobehavioral deficits, cardiovascular parameters, plasma renin, plasma aldosterone levels and renal pathology were determined in stroke-prone spontaneously hypertensive rats. Stroke-prone spontaneously hypertensive rats were allowed access to 1% NaCl as the drinking solution and a high fat diet supplemented with carvedilol (1200 or 2400 ppm) or propranolol (2400 ppm). The control group consisted of stroke-prone spontaneously hypertensive rats placed on the same diet with no drug supplement. Animals fed propranolol had a blood level of 864 +/- 68 ng/ml, whereas carvedilol-fed animals had blood levels of 24 +/- 4 ng/ml at 1200 ppm and 471 +/- 145 ng/ml at 2400 ppm. Carvedilol and propranolol treatment resulted in significant beta adrenoceptor blockade. Both compounds reduced heart rate, but had no significant effects on systolic arterial blood pressure. Carvedilol- and propranolol-treated animals also exhibited significant, prolonged protection from neurobehavioral deficits and mortality (P < .01). Elevated plasma renin activity and aldosterone levels seen in untreated controls were significantly decreased by propranolol (P < .05), and to a considerably greater extent by the same dose of carvedilol (P < .01). Carvedilol decreased renal histopathological damage and cardiac hypertrophy to a greater extent (P < .01) than propranolol (at equal doses). Both carvedilol (P < .01)- and propranolol (P < .01)-treated animals had considerably reduced renal damage at 18 weeks of treatment. Carvedilol reduced renal damage more than propranolol (P < .05). In addition, the lower (1200 ppm) dose of carvedilol, which decreased neurobehavioral deficits and mortality, had no significant effects on organ mass or renal function, but significantly (P < .01) reduced renal damage. These data indicate that both beta adrenoceptor blockers, especially carvedilol to a considerably greater degree, convey significant protection in a genetic model of severe hypertension that results in renal and cardiovascular organ pathology, neurobehavioral deficits and premature death.
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PMID:Chronic carvedilol reduces mortality and renal damage in hypertensive stroke-prone rats. 893 Feb 4

Carvedilol is a novel, multiple-action cardiovascular drug that is currently approved in many countries for the treatment of hypertension. The reduction in blood pressure produced by carvedilol results primarily from beta-adrenoceptor blockade and vasodilation, the latter resulting from alpha 1-adrenoceptor blockade. These actions, as well as several of the other activities of carvedilol, are associated with cardioprotection in animal models that occurs to a degree that is greater than that observed with other drugs. The multiple actions of carvedilol may also provide the underlying rationale for the use of the drug in the treatment of coronary artery disease and congestive heart failure. By virtue of being both a beta-blocker and a vasodilator, carvedilol significantly decreases myocardial work by reducing all three components of myocardial oxygen demand, namely, heart rate, contractility, and wall tension. The vasodilatory effects of carvedilol reduce afterload, and the resulting decrease in impedance to left ventricular ejection offsets the negative inotropic effect that would normally result from beta-blockade. As a consequence, stroke volume and cardiac output are maintained or even increased in animals and in patients with congestive heart failure who are treated with carvedilol. Carvedilol and several of its metabolites are potent antioxidants, and this activity may account, in part, for the cardioprotective effects of the drug observed in animal models of acute myocardial ischemia and, in theory, could also serve to protect the myocardium of patients with hypertension, coronary artery disease, and congestive heart failure, in which oxidative stress is now recognized to occur. The antioxidant effects of carvedilol may both inhibit the direct cytotoxic actions of reactive oxygen radicals and prevent oxygen-radical induced activation of transcription factors and genes associated with inflammatory and remodeling processes. Accordingly, carvedilol inhibits the gene expression of the intracellular adhesion molecule-1 (ICAM-1), an adhesion molecule for polymorphonuclear leukocytes, which typically infiltrate the myocardium under conditions of ischemia and may exacerbate ischemic injury. The antioxidant activity of carvedilol has been shown to inhibit the oxidation of low density lipoprotein (LDL) in vitro, thereby preventing the formation of this cytotoxic and atherogenic form of LDL. It follows, therefore, that in animal models of hyperlipidemia, carvedilol attenuates aortic lipid accumulation and decreases the aortic content of monocytes and foam cells, and at the same time it has been shown to preserve endothelial integrity and function. These actions of carvedilol are not shared by other beta-blockers or by other drugs currently used in the management of hypertension, coronary artery disease, or congestive heart failure. The multiple actions of carvedilol may provide the underlying pharmacologic rationale for the use of this drug in the treatment of patients with coronary artery disease or congestive heart failure, and these actions may account, at least in part, for the reduction in mortality produced by carvedilol in clinical trials involving patients with congestive heart failure. Likewise, these actions of carvedilol may also provide protection, beyond that afforded from reduction in blood pressure, against secondary organ damage in hypertensive patients treated with the drug.
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PMID:Pharmacology of carvedilol: rationale for use in hypertension, coronary artery disease, and congestive heart failure. 921 Oct 17

Carvedilol competitively blocks beta 1, beta 2 and alpha 1 receptors. The drug lacks sympathomimetic activity and has vasodilating properties that are exerted primarily through alpha 1-blockade. Animal models indicate that carvedilol confers protection against myocardial necrosis, arrhythmia and cell damage caused by oxidising free radicals, and the drug has no adverse effects on plasma lipid profiles. Recent data have confirmed the antihypertensive efficacy of carvedilol in patients with mild to moderate essential hypertension. Carvedilol has similar efficacy to other beta-blocking agents, calcium antagonists, ACE inhibitors and hydrochlorothiazide. Carvedilol also improves exercise tolerance and ischaemic symptoms in patients with stable angina pectoris. Significant reductions in serious cardiac events after acute myocardial infarction and in frequency and severity of ischaemic events in patients with unstable angina have also been demonstrated. Interest in the use of carvedilol in patients with congestive heart failure (CHF) has culminated in the publication of a cumulative analysis of data from 1094 patients with mild to severe CHF who participated in the US Carvedilol Heart Failure Study Program (4 trials). After a median follow-up of 6.5 months, a significant overall reduction in mortality relative to placebo (3.2 vs 7.8%) was revealed in patients who had received carvedilol 6.25 to 50 mg twice daily (plus diuretics and ACE inhibitors). All-cause mortality, risk of hospitalisation for cardiovascular reasons and hospitalisation costs were also reduced significantly (by 65, 28% and 62%, respectively) in these trials. In addition, the Australia and New Zealand Heart Failure Research Collaborative Group showed a 26% reduction in the combined risk of death or hospitalisation with carvedilol 12.5 to 50 mg/day relative to placebo after a mean 19-month follow-up period in 415 patients with CHF (relative risk 0.74). Adverse events with carvedilol appear to be less frequent than with other beta-blocking agents, are dosage-related and are usually seen early in therapy. Events most commonly reported are related to the vasodilating (postural hypotension, dizziness and headaches) and the beta-blocking (dyspnoea, bronchospasm, bradycardia, malaise and asthenia) properties of the drug. Carvedilol appears to date to have little effect on the incidence of worsening heart failure. Concomitant administration of carvedilol with some medications requires monitoring. Carvedilol is therefore likely to have a beneficial role in the management of controlled CHF, but further clinical studies are required to show the place of beta-adrenoceptor blocking therapy in general in this indication, and the position of carvedilol relative to other similar agents. Carvedilol is also confirmed as effective in the management of mild to moderate hypertension and ischaemic heart disease.
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PMID:Carvedilol. A reappraisal of its pharmacological properties and therapeutic use in cardiovascular disorders. 921 Oct 87

Carvedilol is a non selective beta-adrenoceptor antagonist which also causes peripheral vasodilation primarily via alpha 1-adrenergic blockade (Strein et al., 1987, McTavish et al., 1993). It has been shown effective in the treatment of mild-to-moderate hypertension and angina, and is currently under investigation in patients with congestive heart failure.
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PMID:Carvedilol overdose. 938 94


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