Augmentation of renal blood flow and sodium excretion in hypertensive patients during blood pressure reduction by intravenous administration of the dopamine1 agonist fenoldopam.

Murphy, Michael B.; McCoy, C E; Weber, Roy R.; Frederickson, E D; Douglas, Frank L.; Goldberg, Leon I.

doi:10.1161/01.cir.76.6.1312

Cited by 109 publications

(56 citation statements)

References 24 publications

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“…22,51,52 Fenoldopam does increase inulin clearance in hypertensive humans. 53 Fenoldopam's natriuretic effect on a HS diet is related, perhaps, to decreased proximal and distal sodium transport, as shown previously. 22,24,32 Enalapril did not cause natriuresis on either diet at the dose employed.…”

Section: Discussionsupporting

confidence: 60%

The Renin-Angiotensin and Renal Dopaminergic Systems Interact in Normotensive Humans

Natarajan¹,

Eisner

Armando³

et al. 2016

Journal of the American Society of Nephrology

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The renin-angiotensin-aldosterone (RAAS) and renal dopaminergic systems interact to maintain sodium balance. High NaCl intake increases renal synthesis of dopamine and dopaminergic receptor activity, decreasing epithelial sodium transport, whereas sodium deficit activates the RAAS, increasing epithelial sodium transport. We tested the hypothesis that attenuation of the natriuretic effect of dopamine D 1 -like receptors during salt restriction results in part from increased RAAS activity in seven salt-resistant normotensive adults using a double-blind placebo-controlled balanced crossover design. All subjects attained sodium balance on low (50 mmol Na + /day) and high (300 mmol Na + /day) NaCl diets, administered 4 weeks apart. Sodium, potassium, lithium, para-aminohippurate, and creatinine clearances were measured before, during, and after a 3-hour infusion of fenoldopam, a D 1 -like receptor agonist, with and without pretreatment with enalapril, an angiotensin converting enzyme inhibitor. On the high NaCl diet, fenoldopam-induced natriuresis was associated with the inhibition of renal proximal and distal tubule sodium transport. On the low NaCl diet, fenoldopam decreased renal distal tubule sodium transport but did not cause natriuresis. The addition of enalapril to fenoldopam restored the natriuretic effect of fenoldopam and its inhibitory effect on proximal tubule sodium transport. Thus, on a high NaCl diet fenoldopam causes natriuresis by inhibiting renal proximal and distal tubule transport, but on a low NaCl diet the increased RAAS activity prevents the D 1 -like receptor from inhibiting renal proximal tubule sodium transport, neutralizing the natriuretic effect of fenoldopam. These results demonstrate an interaction between the renin-angiotensin and renal dopaminergic systems in humans and highlight the influence of dietary NaCl on these interactions. During salt depletion, sodium balance is maintained by increased activity of several systems, including the renin-angiotensin-aldosterone (RAAS) and sympathetic nervous systems.

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Section: Discussionsupporting

confidence: 60%

The Renin-Angiotensin and Renal Dopaminergic Systems Interact in Normotensive Humans

Natarajan¹,

Eisner

Armando³

et al. 2016

Journal of the American Society of Nephrology

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“…However, dobutamine does not act on DA1 receptors and produces much lower increments in renal blood flow than DA. 19,22 Our animals were anesthetized with pentobarbital and were in stable cardiovascular condition, unlike the patients in whom fenoldopam would be administered. Despite these limitations, these data suggest that clinical investigations of the acute administration of fenoldopam alone and in combination will delineate new uses for this compound.…”

Section: Discussionmentioning

confidence: 99%

Cardiovascular and renal hemodynamic effects of intravenous infusions of the selective DA1 agonist, fenoldopam, used alone or in combination with dopamine and dobutamine.

1988

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Fenoldopam (0.1 and 0.2 p,g/kg/min i.v.) was administered to pentobarbital-anesthetized dogs alone and combined with dopamine (DA) and dobutamine. Renal blood flow, heart rate, and mean arterial pressure were measured. Both dosages of fenoldopam increased renal blood flow without altering blood pressure, similar to the effects of DA (1 and 2 ,ug/kg/min). Administration of fenoldopam with only DA (1 ,ug/kg/min) produced further increase in renal blood flow. June 9, 1988. administration is hypotension, which is due to DA1-receptor activation at lower dosages and possibly to a-adrenoceptor antagonist activity at extremely high dosages.10 1' One aim of the present study was to determine in the anesthetized dog the cardiovascular and renal hemodynamic effects of infusion rates of fenoldopam that do not affect or slightly reduce blood pressure. The second goal was to determine whether the effects of DA on cardiac contractile force, heart rate, blood pressure, and renal hemodynamics would be altered by fenoldopam. A third protocol was used to investigate the effects of fenoldopam on cardiovascular and renal responses of dobutamine at rates of 2 and 4 tg/kg/min. Dobutamine

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“…105 Intravenous administration of fenoldopam to hypertensive patients leads to an immediate lowering of blood pressure that is accompanied by increases in RBF as well as sodium and water excretion, and these effects of the compound are maintained throughout the infusion period. 106 A comparative study of fenoldopam with nitroprusside in patients with hypertensive crisis revealed that while both of these compounds caused a prompt lowering of blood pressure, the additional beneficial effect seen with fenoldopam was that it promoted natriuresis and diuresis in these patients. 107 Because RBF was not measured in this study, it is not clear whether natriuretic response was secondary due to an increase in RBF or whether it resulted from the direct tubular action of fenoldopam on D 1 -like dopamine receptors.…”

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confidence: 99%

Renal Dopamine Receptor Function in Hypertension

1998

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Abstract-Dopamine plays an important role in the regulation of renal sodium excretion. The synthesis of dopamine and the presence of dopamine receptor subtypes (D 1A , D 1B as D 1 -like and D 2 , and D 3 as D 2 -like) have been shown within the kidney. The activation of D 1 -like receptors located on the proximal tubules causes inhibition of tubular sodium reabsorption by inhibiting Na,H-exchanger and Na,K-ATPase activity. The D 1 -like receptors are linked to the multiple cellular signaling systems (namely, adenylyl cyclase, phospholipase C, and phospholipase A 2 ) in the different regions of the nephron. Defective renal dopamine production and/or dopamine receptor function have been reported in human primary hypertension as well as in genetic models of animal hypertension. There may be a primary defect in D 1 -like receptors and an altered signaling system in the proximal tubules that lead to reduced dopamine-mediated effects on renal sodium excretion in hypertension. Recently, it has been shown in animal models that the disruption of either D 1A or D 3 receptors at the gene level causes hypertension in mice. Dopamine and dopamine receptor agonists also provide therapeutic potential in treatment of various cardiovascular pathological conditions, including hypertension. However, because of the poor bioavailability of the currently available compounds, the use of D 1 -like agonists is limited to the management of patients with severe hypertension when a rapid reduction of blood pressure is clinically indicated and in acute management of patients with heart failure. In conclusion, there is convincing evidence that dopamine and dopamine receptors play an important role in regulation of renal function, suggesting that a defective dopamine receptor/signaling system may contribute to the development and maintenance of hypertension. Further studies need to be directed toward establishing a direct correlation between defective dopamine receptor gene in the kidney and development of hypertension. Subsequently, it may be possible to use a therapeutic approach to correct the defect in dopamine receptor gene causing the hypertension. (Hypertension. 1998;32:187-197.)Key Words: dopamine Ⅲ receptors, dopamine Ⅲ kidney tubules, proximal Ⅲ kidney Ⅲ hypertension, renal D opamine is known to play an important role in the control of renal sodium excretion. Specific receptors for dopamine have been identified in various regions of the nephron, and it is reported that dopamine is synthesized within the renal proximal tubules. Endogenously produced dopamine, as well as exogenously administered dopamine, exerts pronounced effects on renal function. There are reports suggesting that a defect in renal dopamine receptor function and/or dopamine production may play a role in the pathogenesis of hypertension. For example, reduced urinary dopamine/ sodium excretion is reported in some forms of human primary hypertension. [1][2][3] It is reported that a defect in dopamine receptor-G protein coupling and alterations in the signaling component...

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Augmentation of renal blood flow and sodium excretion in hypertensive patients during blood pressure reduction by intravenous administration of the dopamine1 agonist fenoldopam.

Cited by 109 publications

References 24 publications

The Renin-Angiotensin and Renal Dopaminergic Systems Interact in Normotensive Humans

The Renin-Angiotensin and Renal Dopaminergic Systems Interact in Normotensive Humans

Cardiovascular and renal hemodynamic effects of intravenous infusions of the selective DA1 agonist, fenoldopam, used alone or in combination with dopamine and dobutamine.

Renal Dopamine Receptor Function in Hypertension

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