Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.15.1 (ACE)
 18,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

Experiments were performed in anaesthetized dogs to characterize the renal effects of the selective dopamine DA1-receptor agonist, fenoldopam. Intrarenal artery infusion of fenoldopam (0.01-10 micrograms/kg per min) caused dose-related renal vasodilation. At low doses (0.01-0.3 micrograms/kg per min), renal vasodilation occurred without concomitant falls in blood pressure but was accompanied by increased urine output. This diuresis was most probably a result of reduced tubular reabsorption since glomerular filtration rate was not increased. Both fenoldopam-induced renal vasodilation and diuresis were blocked to a similar extent by the selective dopamine DA1-receptor antagonist, SCH 23390 (30 micrograms/kg, intravenously), suggesting that both effects were mediated by dopamine DA1-receptors. In the presence of the angiotensin converting enzyme inhibitor, captopril (1 mg/kg, intravenously, + 20 micrograms/kg per min, intrarenal artery), fenoldopam (0.01-0.3 micrograms/kg per min) significantly increased fractional excretion of sodium, despite reducing blood pressure; neither of these effects were observed in captopril-free dogs. These observations support the view that the inhibitory effect of fenoldopam on tubular function, and its vasodepressor activity, may be opposed by angiotensin II resulting from fenoldopam-induced renin release.
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PMID:Effects of dopamine DA1-receptor blockade and angiotensin converting enzyme inhibition on the renal actions of fenoldopam in the anaesthetized dog. 168 41

The effects of a single dose of ibopamine on renal haemodynamics, sodium excretion, blood pressure (BP) and heart rate (HR) were investigated in 10 patients (aged 52-82 years) with severe congestive heart failure (CHF) who were in NYHA class IV. All patients used ACE inhibitors, digoxin and diuretics. After determining baseline values, ibopamine 100 mg was administered. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured simultaneously using radio pharmaceuticals. An increase in GFR and ERPF was observed during 3 and 2 h, with a maximum of 15 and 11%, respectively. The ratio GFR/ERPF representing the filtration fraction (FF) was markedly elevated at baseline, 34%, and remained unchanged. No clinically significant increase of sodium excretion was found. No changes in blood pressure, heart rate, plasma renin activity (PRA) and aldosterone or norepinephrine were observed. We conclude that ibopamine increases both ERPF and GFR in patients with severe CHF, possibly as a consequence of both inotropic cardiac and specific renal effects with equal preglomerular and postglomerular vasodilation. The lack of the presumed fall in FF may be the consequence of the expected DA1-induced renal vasodilation, partially reversed by the alpha adrenergic properties of ibopamine for this dose. Ibopamine caused no clinically significant natriuresis in these salt-depleted patients. No changes in PRA, aldosterone and catecholamines were found.
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PMID:Effects of ibopamine on renal haemodynamics in patients with severe congestive heart failure. 809 55

Although systemic hypertension is a common clinical disorder, hypertensive emergencies are unusual in clinical practice. Situations that qualify as hypertensive emergencies include accelerated or malignant hypertension, hypertensive encephalopathy, acute left ventricular failure, acute aortic dissection, pheochromocytoma crisis, interaction between tyramine-containing foods or drugs and monoamine oxidase inhibitors, eclampsia, drug-induced hypertension and possibly intracranial hemorrhage. It is important to recognize these conditions since immediate lowering of systemic blood pressure is indicated. The diagnosis of hypertensive emergencies depends on the clinical manifestations rather than on the absolute level of the blood pressure. Depending on the target organ that is affected, the manifestations of hypertensive emergencies can be quite expressive, yet variable. Thus, the physician has to make the clinical diagnosis urgently in order to render appropriate therapy. Several parenteral drugs can quickly and effectively lower the blood pressure in hypertensive emergencies. Intravenous fenoldopam, a selective dopamine (DA1) receptor agonist, offers the advantage of improving renal blood flow and causing natriuresis. Intravenous nicardipine may be beneficial in reserving tissue perfusion in patients with ischemic disorders. Whereas trimethaphan camsilate is the drug of choice for managing acute aortic dissection, hydralazine remains the drug of choice for the treatment of eclampsia. The alpha-adrenoceptor, phentolamine, is useful in patients with pheochromocytoma crisis. Enalaprilat is the only ACE inhibitor available for parenteral use and may be particularly useful in treating hypertensive emergencies in patients with heart failure. However, ACE inhibitors may cause a precipitous fall in blood pressure in patients who are hypovolemic. Although useful as adjunctive therapy in hypertensive crises, diuretics should be used with caution in these patients because prior volume depletion may be present in some conditions such as malignant hypertension. The treating physician should be familiar with the pharmacological and clinical actions of drugs which are indicated for and useful in the treatment of hypertensive emergencies. Once the patient's situation has stabilized, the patient may be switched to an oral medication and the physician should discuss long term follow up plans. With appropriate clinical diagnosis, hypertensive emergencies can be successfully treated and the complications can be prevented with timely intervention.
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PMID:Hypertensive emergencies. Etiology and management. 1472 43