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

Fenoldopam is a dopamine agonist that causes peripheral vasodilation via stimulation of dopamine 1 (D1) receptors. The efficacy of an intravenous infusion of fenoldopam in decreasing blood pressure in patients with a hypertensive urgency, including patients who developed hypertension after coronary artery bypass graft surgery, and in a small number of patients with hypertensive emergency, is similar to that of sodium nitroprusside. However, unlike sodium nitroprusside, fenoldopam also increases renal blood flow and causes diuresis and natriuresis. There is no evidence of rebound hypertension after stopping the infusion. As the tolerability profile of fenoldopam is generally similar to that of sodium nitroprusside, fenoldopam appears to be an effective alternative to sodium nitroprusside in the immediate treatment of patients who develop severe hypertension and in whom oral treatment is not practical. Fenoldopam may be particularly useful in patients who develop hypertension after coronary artery bypass graft surgery, but further studies are required to confirm its role in hypertensive emergency.
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PMID:Fenoldopam: a review of its pharmacodynamic and pharmacokinetic properties and intravenous clinical potential in the management of hypertensive urgencies and emergencies. 933 65

Fenoldopam is a selective dopamine agonist that is being considered for the parenteral treatment of systemic hypertension. In both an oral and parenteral form, the drug causes peripheral vasodilation by stimulating dopamine-1 adrenergic receptors. Its pharmaco-dynamics are reviewed in this article, along with the clinical experiences in patients with hypertensive urgencies and emergencies. Intravenous fenoldopam may provide advantages over sodium nitroprusside because it can induce both a diuresis and natriuresis, is not light sensitive, and is not associated with cyanide toxicity. There is no evidence for rebound hypertension after discontinuation of fenoldopam influsion.
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PMID:Fenoldopam: a new dopamine agonist for the treatment of hypertensive urgencies and emergencies. 959 53

A number of new classes of antihypertensive drugs have become available in the recent years which appear to hold therapeutic potential for better management of hypertension. Losartan, an angiotensin II receptor antagonist, does not produce cough which is classically seen with ACE inhibitors. Fenoldopam, a dopamine D1-receptor agonist, has a rapid and short duration of action and is ideally suited by intravenous infusion for quick control of BP in hypertensive emergencies. Kentaserin, a serotonin (5-HT2A) receptor antagonist, has a long duration of action and can be given once daily. It has the added benefit of having antiplatelet effect. Monatepil, a dual alpha-receptor and calcium channel blocker, has potent antihypertensive effect, lowers serum cholesterol and also has antiatherosclerotic effect. Dual ACE and endopeptidase inhibitor, such as alatriopril, has a "broad spectrum" antihypertensive effect and may be effective in majority of hypertensive patients. Many other classes of antihypertensive drugs are still in the investigative stage, and their therapeutic potentials and safety need to be ascertained in long-term controlled clinical trials.
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PMID:New classes of antihypertensive drugs: therapeutic potentials. 1005 49

Eight patients with stage I-II hypertension received a continuous IV infusion of the selective dopamine-1 agonist, fenoldopam, for up to 48 hours at rates from 0.4 to 1.9 micrograms/kg/min. Hemodynamics and clinical symptoms during infusion were compared to the same parameters in the 24-hour periods before and after infusion. Fenoldopam lowered blood pressure and increased heart rate. Greatest changes occurred during the first 12 hours of infusion and gradually returned toward preinfusion values throughout the remaining 36 hours in the six patients who completed 48 hours of infusion. Fenoldopam was discontinued within 2 hours of starting the infusion in two patients who received drug rates of 0.9 microgram/kg/min and 1.9 micrograms/kg/min because of precipitous bradycardia. Clinical symptoms noted at fenoldopam doses higher than 0.8 microgram/kg/min were headache, dizziness, diaphoresis, nausea and vomiting, and restlessness. In this pilot study, fenoldopam effectively reduced blood pressure in patients with stage I-II hypertension for up to 48 hours, but fixed-dose infusion rates above 0.8 microgram/kg/min were associated with a high frequency of clinically significant and often intolerable adverse effects.
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PMID:Sustained hemodynamic effects of the selective dopamine-1 agonist, fenoldopam, during 48-hour infusions in hypertensive patients: a dose-tolerability study. 1023 94

A panel of clinicians from anesthesiology, surgery, nephrology, hypertension, cardiology, and pharmacology was convened to discuss pharmacologic therapeutics in the management of hypertensive crisis and perioperative hypertension. The panel discussed the advantages and limitations of currently available parenteral drugs, and assessed the potential use of fenoldopam mesylate, a drug in clinical development since 1981, and recently approved by the U.S. Food and Drug Administration (FDA). Fenoldopam is a dopamine receptor (DA1 selective) agonist that is a systemic and renal vasodilator. It was concluded that fenoldopam offers significant advantages as a parenterally administered agent for the management of blood pressure in both hypertensive emergencies and in the perioperative setting.
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PMID:Fenoldopam: a new parenteral antihypertensive: consensus roundtable on the management of perioperative hypertension and hypertensive crises. 1041 62

The impaired renal paracrine function of dopamine in spontaneously hypertensive rats (SHR) is caused by hyperphosphorylation and desensitization of the renal D(1) dopamine receptor. Protein phosphatase 2A (PP(2A)) is critical in the regulation of G-protein-coupled receptor function. To determine whether PP(2A) expression and activity in the kidney are differentially regulated in genetic hypertension, we examined the effects of a D(1)-like agonist, fenoldopam, in renal cortical tubules and immortalized renal proximal tubule cells from normotensive Wistar-Kyoto rats (WKY) and SHR. In cortical tubules and immortalized proximal tubule cells, PP(2A) expression and activities were greater in cytosol than in membrane fractions in both WKY and SHR. Although PP(2A) expressions were similar in WKY and SHR, basal PP(2A) activity was greater in immortalized proximal tubule cells of SHR than WKY. In immortalized proximal tubule cells of WKY, fenoldopam increased membrane PP(2A) activity and expression of the regulatory subunit PP(2A)-B56alpha, effects that were blocked by the D(1)-like antagonist SCH23390. Fenoldopam had no effect on cytosolic PP(2A) activity but decreased PP(2A)-B56alpha expression. In contrast, in immortalized proximal tubule cells of SHR, fenoldopam decreased PP(2A) activity in both membranes and cytosol but predominantly in the membrane fraction, without affecting PP(2A)-B56alpha expression; this effect was blocked by the D(1)-like antagonist SCH23390. We conclude that renal PP(2A) activity and expression are differentially regulated in WKY and SHR by D(1)-like receptors. A failure of D(1)-like agonists to increase PP(2A) activity in proximal tubule membranes may be a cause of the increased phosphorylation of the D(1) receptor in the SHR.
Hypertension 2000 Dec
PMID:Renal protein phosphatase 2A activity and spontaneous hypertension in rats. 1111 24

We have studied the effect of chronic treatment with dopamine D1 receptor agonist fenoldopam (1 mg/kg, i.p. daily for 6 weeks) on renal function and metabolic parameters in streptozotocin (STZ)-diabetic rats. Diabetes was induced by a single tail vein injection of STZ (45 mg/kg). STZ produced severe hyperglycemia, hypoinsulinemia, hypercholesterolemia, hypertriglyceridemia, hypertension and bradycardia. Fenoldopam treatment significantly reduced fasting but not fed blood glucose levels and lowered the blood pressure in diabetic animals. Significant change was not observed in insulin, cholesterol, triglyceride levels. Diabetic animals showed increase in AUCglucose and decrease in AUCinsulin during oral glucose tolerance test. Fenoldopam treatment did not significantly change these values in diabetic animals. STZ produced increase in serum urea, creatinine and blood urea nitrogen. Diuresis and urinary sodium retention was observed in diabetic animals. Renal hypertrophy was observed as seen from increased kidney weight/body weight ratio and increased total RNA content as well as decreased total DNA content. Fenoldopam treatment significantly lowered serum urea, creatinine and blood urea nitrogen. Urinary sodium retention was significantly reduced and renal hypertrophy was prevented with fenoldopam treatment as seen from the improved kidney weight/body weight ratio. Fenoldopam treatment significantly prevented reduction in total DNA content and increase in total RNA content further substantiating reduced renal hypertrophy. Our data suggest that STZ induced diabetes is associated with renal dysfunctions and fenoldopam treatment could be beneficial in a condition where diabetes mellitus co-exists with hypertension and compromised renal function.
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PMID:Beneficial effects of fenoldopam treatment on renal function in streptozotocin-induced diabetic rats. 1188 92

In the periphery, physiological dopamine increases renal blood flow, decreases renal resistance and acts on the kidney tubule to enhance natriuresis and diuresis. The loss of dopamine function may be involoved in the deterioration in kidney function associated with ageing and may have a role in the pathogenesis of hypertension and diabetes. Intravenous dopamine is used as a positive inotrope in the treatment of acute heart failure and cardiogenic shock and as a diuretic in renal failure. The clinical uses of dopamine are limited, as it must be given intravenously, and also has widespread effects. The levels of peripheral dopamine can be increased by the administration of L-dopa to increase synthesis, prodrugs to release dopamine (docarpamine, glu-dopa) or by inhibiting the breakdown of dopamine (nitecapone). Preliminary clinical trials suggest that docarpamine may be useful in patients with low cardiac output syndrome after cardiac surgery and in refractory cirrhotic ascites. Ibopamine is an agonist at dopamine D1 and D2 receptors, which may retard the progression of chronic renal failure. Glu-dopa is selective for the kidney, thus avoiding widespread side effects. The early clinical studies with ibopamine as a diuretic in heart failure were favourable but the subsequent large mortality study showed that ibopamine increased mortality. Fenoldopam is a selective dopamine D1 receptor agonist. Intravenous fenoldopam may be useful in the treatment of hypertension associated with coronary artery bypass surgery or in hypertensive emergencies. Although our understanding of physiological and pathological roles of peripheral dopamine has been increasing rapidly in recent times, we still need more information to allow the design of clinically useful drugs that modify these roles. One priority is an orally-active selective dopamine D1 receptor agonist.
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PMID:The therapeutic potential of dopamine modulators on the cardiovascular and renal systems. 1199 45

A protocol for using fenoldopam, an FDA-approved intravenous agent for the treatment of severe hypertension with a newly available renal vasodilatory effect, was adopted to prevent radiocontrast nephropathy in high-risk patients undergoing angiographic procedures. Fenoldopam is a selective dopamine-receptor agonist with renoprotective properties. The results of 46 consecutive procedures were retrospectively reviewed in both diabetic and nondiabetic patients and compared to a prior published cohort of similarly at-risk patients. The incidence of radiocontrast nephropathy was 13% in the group treated with fenoldopam, compared to an expected 38% based on historical controls. The percentage change in serum creatinine was also very favorable. In this clinical experience of a high-volume coronary and peripheral vascular laboratory, the use of fenoldopam in high-risk patients appeared to minimize the likelihood of radiocontrast nephropathy.
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PMID:Clinical experience with the use of fenoldopam for prevention of radiocontrast nephropathy in high-risk patients. 1243 65

Radiocontrast-induced nephropathy develops in approximately 10% to 20% of patients following administration of iodine-based dye and is one of the most prognostically detrimental complications that invasive cardiologists and radiologists encounter. Preexisting renal dysfunction and diabetes mellitus are two of the most powerful predictors of the likelihood of developing acute renal insufficiency after contrast delivery. To date, only adequate preprocedural hydration and postprocedural hydration to offset dehydration from contrast-induced diuresis have been shown to be effective in preventing this condition. Fenoldopam mesylate, a systemic vasodilator currently FDA-approved for short-term, in-hospital management of severe hypertension, has been shown to increase renal plasma flow in patients with and without chronic renal insufficiency. As a selective agonist of the dopamine-1 receptor, fenoldopam may preserve outer medullary renal blood flow and thereby attenuate radiocontrast-induced nephropathy. Small studies with fenoldopam prior to iodine-based dye administration have demonstrated low rates of radiocontrast nephropathy, and a larger, randomized trial has found that renal blood flow 1 hour after angiography rose in the fenoldopam group compared to a decline in the placebo group. The CONTRAST study has been designed to determine whether fenoldopam is indeed effective in diminishing the occurrence of radiocontrast-induced nephropathy.
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PMID:Design and rationale of CONTRAST--a prospective, randomized, placebo-controlled trial of fenoldopam mesylate for the prevention of radiocontrast nephropathy. 1243 66


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