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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This review discusses the localization of adrenergic- and dopaminergic-adrenoceptors within the cardiovascular system and describes the cardiovascular and renal changes produced following the activation of these receptors by appropriate agonists. Whereas the role of alpha- and beta-adrenergic agents in the treatment of heart failure is well recognized, recent studies with dopamine (DA)-receptor agonists indicate that they offer a novel approach in the therapy of congestive heart failure. DA-adrenoceptor agonists reduce afterload by causing vasodilation and promote sodium excretion via direct activation of DA1-adrenoceptors located on renal tubules. Fenoldopam is a selective DA1-adrenoceptor agonist found to be effective in heart failure. It reduces afterload by causing peripheral vasodilation and produces natriuresis and diuresis. Dopexamine is a DA1- and beta 2-adrenoceptor agonist, and its efficacy in heart failure is due to its ability to provide mild inotropic support and cause a reduction in afterload. Ibopamine is a prodrug that is converted into its active metabolite, epinine. This compound activates primarily DA1- and DA2-adrenoceptors. It is effective in heart failure, and the mechanism progresses via DA1- and DA2-adrenoceptor-mediated reduction in afterload. Agonists of DA2-adrenoceptors reduce afterload by decreasing the release of norepinephrine and by reducing the levels of renin-angiotensin-aldosterone system. Since both of these systems are active in heart failure, ibopamine offers a rational approach for therapy. The present review addresses the concept of pharmacologic intervention in adrenergic and dopaminergic influence in the cardiovascular and renal systems to produce changes that are desirable for the pharmacotherapy of congestive heart failure.
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PMID:Cardiovascular pharmacology of adrenergic and dopaminergic receptors: therapeutic significance in congestive heart failure. 167 49

Ibopamine is an orally active derivative of dopamine (DA) which metabolizes to its active form, epinine. Epinine is one of the few catecholamines that possess dopaminergic--DA1 and DA2--activity, alpha 1, alpha 2, beta 1, and beta 2 activity, with indirect sympathomimetic action of dopamine. Ibopamine increased positive dP/dt, stroke volume, aortic blood flow, renal blood flow, and diuresis in animals. In healthy volunteers and patients with heart failure, a single oral dose of ibopamine showed primary vasodilating action (postsynaptic DA1 activity and presynaptic DA2 activity). Following a single oral dose of 100 or 200 mg of ibopamine, the plasma concentration of epinine reached its peak within 30 minutes, and declined rapidly so that concentration was not detectable after 1.5-3 hours. Pharmacokinetics and hemodynamic effects in congestive heart failure patients are also discussed.
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PMID:Clinical pharmacology of ibopamine. 167 50

The importance of the dopaminergic system in heart failure is unknown and the therapeutic potential of orally active compounds stimulating dopaminergic receptors has yet to be established. Despite similar acute haemodynamic changes in heart failure and despite a comparable profile of receptor stimulation, oral levodopa (the prodrug of dopamine) and oral ibopamine (the prodrug of epinine) produce opposite effects on plasma norepinephrine and have different pharmacokinetics. Placebo-controlled studies indicate a beneficial effect of ibopamine on exercise tolerance in patients with heart failure, whereas invasive evaluation of left ventricular function indicate that at the doses used in these trials, ibopamine does not act as a positive inotropic drug but rather as a vasodilator. This suggests that DA1 and DA2 receptor stimulation may be beneficial in heart failure. Further studies are, however, needed to specify the exact role of this therapeutic approach in comparison with other agents, such as ACE inhibitors, also able to modulate neuro-humoral activation in heart failure.
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PMID:Dopaminergic drugs in the management of chronic heart failure. 168 Jun 85

7,8-Dihydroxy-4-(3,4-dihydroxyphenyl)-1,2,3,4-tetrahydroisoquinoline (1) and 4-(3,4-dihydroxyphenyl)-7-hydroxy-8-methyl-1,2,3, 4-tetrahydroisoquinoline (2) are potent renal vasodilators which selectively stimulate DA1 (peripheral dopamine receptor-1) receptors. Especially, (S)-(-)-1 is the most potent. Its DA1 agonist activity is about 10 times stronger than dopamine for increasing renal blood flow in anesthetized dogs. The renal and cardiovascular effects of (S)-(-)-1 may be suitable for the treatment of patients with renal insufficiency, heart failure and hypertension.
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PMID:Synthesis, resolution, and renal vasodilation activity of novel DA1 agonists: 4-(3,4-dihydroxyphenyl)-1,2,3,4-tetrahydroisoquinoline derivatives. 183 45

Dopamine (DA)--previously regarded simply as the precursor of norepinephrine--is now known to have its own unique effects on cardiovascular regulation which are mediated, in part, by activating specific DA receptors. DA has long been used in the treatment of shock and heart failure. In recent years it has been used at low infusion rates for its renal effects, in combination with other more specific inotropic or pressor agents. Lack of oral bioavailability has limited its use in long-term therapy, however; levodopa and dopa conjugates which are orally absorbed and metabolized to the active form are under investigation. The novel DA1 receptor agonist fenoldopam is claiming a role in the management of hypertension, heart failure, and the preservation of renal function. DA2 receptor agonists are also being evaluated as potential antihypertensive agents.
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PMID:Dopamine and dopamine receptor agonists in cardiovascular therapy. 196 61

Dopexamine hydrochloride is a novel synthetic catecholamine, structurally related to dopamine, with marked intrinsic agonist activity at beta 2-adrenoceptors, lesser agonist activity at dopamine DA1- and DA2-receptors and beta 1-adrenoceptors, and an inhibitory action on the neuronal catecholamine uptake mechanism. The drug is administered by intravenous infusion, and is characterized by a rapid onset and short duration of action. Short term haemodynamic studies in volunteers and patients with severe chronic heart failure have indicated that dopexamine hydrochloride reduces afterload through pronounced arterial vasodilatation, increases renal perfusion by selective renal vasodilation and evokes mild cardiac stimulation through direct and indirect positive inotropism. Preliminary small-scale noncomparative studies indicate that dopexamine hydrochloride displays beneficial haemodynamic effects in patients with acute heart failure and those requiring haemodynamic support following cardiac surgery, and that these effects are substantially maintained during longer term administration (less than or equal to 24 hours). Dopexamine hydrochloride appears to be generally well tolerated. Nausea and vomiting are the most frequently reported adverse effects, and respond to dosage reduction. Occasional reports of chest pain/angina pectoris precipitated by tachycardia indicates the need for caution in the use of dopexamine hydrochloride in patients with ischaemic heart disease. Thus, dopexamine hydrochloride may prove to be a useful alternative to dopamine and dobutamine in the treatment of acute heart failure and the postoperative management of low cardiac output states, although controlled studies are required to establish its efficacy and tolerability with respect to that of established therapies.
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PMID:Dopexamine hydrochloride. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic potential in acute cardiac insufficiency. 197 Feb 88

The existence of two dopamine receptor subtypes (DA1 and DA2) has been firmly established. Activation of DA1 receptors is associated with vasodilation, primarily in the renal, mesenteric, cerebral, and coronary arterial beds, and a natriuresis. DA2 receptors located on postganglionic sympathetic nerves and sympathetic ganglia mediate a decrease in the release of norepinephrine from sympathetic nerve terminals. The DA receptor activity of dopamine (which activates beta 1- and alpha-adrenoceptors as well as DA receptors) plays a prominent role in determining the beneficial hemodynamic responses to this drug in patients with heart failure. As a result, recent research efforts have been directed toward the development of dopamine analogues, which are orally effective and exhibit more selective agonist activity at DA receptors. Limited clinical experience in heart failure is now available for analogues with different spectra of receptor activity than dopamine, including selective DA1 and DA2 agonists. A review of these data is presented with an attempt to define the clinical relevance of the DA receptor-agonist properties of the compounds. Although the results of early clinical studies with some of these first-generation dopamine congeners are encouraging, analysis of ongoing large-scale placebo-controlled trials will provide valuable insight into their utility as therapeutic agents for patients with heart failure.
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PMID:Role of dopamine receptors and the utility of dopamine agonists in heart failure. 197 45

In eight patients (63 +/- 8 years) with dilated cardiomyopathy, the acute effects of positive inotropic stimulation with dopexamine hydrochloride, a beta-2-agonistic and DA1-dopaminergic catecholamine, on the plasma levels of ANP and cGMP were tested. A four-point dose-response curve was prepared for dopexamine from 1 microgram/kg/min to 4 micrograms/kg/min. Each infusion stage lasted 15 min; ANP and cGMP were taken from the mixed venous blood. Hemodynamic parameters were determined by a Swan-Ganz catheter; cardiac output was determined by thermodilution. ANP dropped by 40% from 348 +/- 124 pg/ml to 208 +/- 70 pg/ml (p less than or equal to 0.01), while cGMP dropped by 25% from 4.8 +/- 1.6 pmol to 3.6 +/- 1.3 pmol/ml at the time of maximum hemodynamic effect after 1 h. Linear regression analyses revealed a significant relationship (p less than or equal to 0.01) between ANP as the independent variable and cGMP as the dependent variable. The hemodynamic determinants of the ANP concentration proved to be--independently of each other--the pulmonary capillary wedge pressure (p less than or equal to 0.01) and the mean right atrial pressure (p less than or equal to 0.01). The results show that chronically elevated ANP and cGMP levels can be strikingly reduced within a short time, whereby ANP and cGMP show similar kinetics. The results suggest a use of ANP and cGMP as humoral parameters in the therapy control of chronic heart failure.
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PMID:[Acute reduction of increased atrial natriuretic peptide level and cyclic guanosine monophosphate in patients with chronic heart failure caused by beta-adrenergic stimulation with dopexamine hydrochloride. Correlation with hemodynamic parameters]. 197 99

Dopexamine hydrochloride is a novel compound with properties of DA1-dopaminergic and beta 2-adrenergic receptor agonism and neuronal noradrenaline uptake inhibition. It has been shown to produce beneficial renal and haemodynamic effects in patients with severe heart failure. We compared the haemodynamic effects of dopexamine (0.5 to 6 micrograms/kg/min) with those of dobutamine (5 to 25 micrograms/kg/min) in 9 patients with severe congestive heart failure. The two drugs were similar in their effects at peak infusion rates: heart rate increased (dopexamine 87 +/- 17 to 100 +/- 14; dobutamine 91 +/- 18 to 103 +/- 17 min-1), cardiac index increased (dopexamine 1.7 +/- 0.5 to 2.8 +/- 1.1; dobutamine 1.8 +/- 0.5 to 3.0 +/- 1.1 l.min-1.m-2) and systemic vascular resistance decreased (dopexamine 1553 +/- 221 to 1117 +/- 432; dobutamine 1721 +/- 347 to 1280 +/- 433 dyne.s.cm-5). Neither drug affected pulmonary artery wedge pressure (dopexamine 24 +/- 6 to 22 +/- 6; dobutamine 25 +/- 9 to 24 +/- 10 mm Hg). Dopexamine had significantly lower peak effects on left ventricular stroke work index (dopexamine 20 +/- 9, dobutamine 27 +/- 15 g.m.m-2, P less than 0.05) and cardiac power output (dopexamine 0.71 +/- 0.36, dobutamine 0.93 +/- 0.46 W, P less than 0.05). These haemodynamic effects, due largely to vasodilatation but with some contributory positive inotropy, indicate that dopexamine will be useful in the acute treatment of congestive heart failure.
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PMID:Comparison of the haemodynamic effects of dopexamine and dobutamine in patients with severe congestive heart failure. 201 Feb 43

In the sympathetic nervous system the physiologic effects of the endogenous catecholamines noradrenaline (NA) and adrenaline (A) are mediated by alpha- and beta-adrenoreceptors (ARs). Both AR-types can be subdivided into two major subtypes: alpha-ARs into alpha-1 (predominant effect: vasoconstriction) and alpha-2 (presynaptic: inhibition of NA-release; postsynaptic: vasoconstriction), beta-ARs into beta-1 (cardiac effects, renal renin release, and lipolysis) and beta-2 (presynaptic: facilitation of NA-release; postsynaptic: vascular, bronchial, and uterine smooth muscle relaxation, glycogenolysis and possibly part of the A-mediated cardiac effects). During the last 30 years growing evidence has accumulated that dopamine (DA), the third endogenous catecholamine and the immediate precursor of NA, may also cause peripheral effects through stimulation of specific DA-receptors, in addition to its known action at alpha- and beta-ARs. It is now well accepted that at least two different DA-receptors are present in many peripheral tissues (DA1 and DA2), including those of the cardiovascular and autonomic nervous system. They seem to be involved in dilation of certain vascular beds, inhibition of NA-release during nerve stimulation, natriuresis, and aldosterone release. In chronic heart failure cardiac beta-AR function decreases (presumably due to endogenous "down-regulation" by the elevated catecholamines), and this decrease is related to the severity of heart failure (judged clinically by New York Heart Association functional class). The human heart contains both functional beta-1 and beta-2 ARs; cardiac beta-1 and beta-2 ARs seem to be differentially affected by different kinds of heart failure; in end-stage dilated cardiomyopathy beta-1 ARs are selectively reduced, whereas beta-2 ARs are nearly normal.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Physiology and pharmacology of cardiovascular catecholamine receptors: implications for treatment of chronic heart failure. 224 13


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