Effect of Felodipine on Renal Hemodynamics and Excretion in the Dog

Ek, Bengt; Sjölander, May; DiBona, Gerald F.; Hallbäck-Nordlander, Margareta; Ljung, Bengt

doi:10.3181/00379727-179-42086

Experimental Biology and Medicine

1985

DOI: 10.3181/00379727-179-42086

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Effect of Felodipine on Renal Hemodynamics and Excretion in the Dog

Bengt Ek¹,

May Sjölander²,

Gerald F. DiBona³

et al.

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1985

1994

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Cited by 5 publications

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“…However, the mechanisms responsible for CEBmediated natriuresis remain unknown. Since selective administration of a CEB into the renal artery stimulates natriuresis, 10 an interaction with intrarenal natriuretic systems such as the dopaminergic system 11 could be involved.We and others have observed that the increased sodium excretion during calcium entry blockade is not accompanied by a parallel increase of potassium excretion. ,6,i2 This is rather surprising in view of the aforementioned CEB-mediated decrease of proximal tubular sodium reabsorption.…”

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Metoclopramide stimulates kaliuresis during felodipine without affecting its natriuresis.

et al. 1994

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Calcium entry blockers such as felodipine induce natriuresis without a parallel rise of potassium excretion. Previous studies with exogenous aldosterone and felodipine have suggested that the absence of kaliuresis might be explained by a felodipine-induced inhibition of aldosterone release. The natriuresis with calcium entry blockers could not be attributed to a similar mechanism but might be due to the stimulation of intrarenal natriuretic systems such as the dopaminergic system. We studied whether the aselective dopamine antagonist metoclopramide prevents the natriuresis with low and therapeutic felodipine doses and whether metoclopramide-induced aldosterone release promotes kaliuresis with felodipine. Twelve healthy male volunteers participated in a randomized, placebocontrolled, crossover study comparing felodipine infusion during metoclopramide with felodipine alone. Metoclopramide had no significant influence on the pronounced and dose-dependent increases of renal plasma flow and urinary sodium excretion with C alcium ehtry blockers (CEBs), especially dihydropyridines such as felodipine, are powerful vasodilating drugs useful for the treatment of hypertension.1 These drugs have short-term diuretic and natriuretic effects, 2 which may contribute to their antihypertensive action. Clearance studies in humans 3 "6 and some micropuncture studies in animals 79 have indicated that CEBs decrease proximal tubular sodium reabsorption. However, the mechanisms responsible for CEBmediated natriuresis remain unknown. Since selective administration of a CEB into the renal artery stimulates natriuresis, 10 an interaction with intrarenal natriuretic systems such as the dopaminergic system 11 could be involved.We and others have observed that the increased sodium excretion during calcium entry blockade is not accompanied by a parallel increase of potassium excretion. ,6,i2 This is rather surprising in view of the aforementioned CEB-mediated decrease of proximal tubular sodium reabsorption. We have previously demonstrated that simultaneous administration of exogenous aldosterone and felodipine was followed by a large increase of kaliuresis.13 Therefore, the attenuation of potassium excretion during calcium entry blockade might be explained by the well-known CEB-mediated inhibition of aldosterone release. © 1994 American Heart Association, Inc.felodipine. Metoclopramide increased plasma aldosterone concentration from 0.17±0.03 to 0.60±0.14 nmol/L, and subsequent felodipine infusion clearly increased urinary potassium excretion by 23 ±6 and 35±8 /xmol/min (low and therapeutic doses, respectively). In contrast, potassium excretion remained stable with felodipine alone (+5±4 and +7±5 /xmol/min, respectively). In conclusion, the natriuretic action of calcium entry blockers cannot be blocked by the aselective dopamine antagonist metoclopramide. This natriuresis is accompanied by kaliuresis only in the presence of elevated endogenous aldosterone concentrations. The ability of calcium entry blockers to prevent a rise of pl...

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Metoclopramide stimulates kaliuresis during felodipine without affecting its natriuresis.

et al. 1994

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The acute renal haemodynamic and endocrine response to felodipine in normal man

Jenkins

Craig

Cumming

et al. 1988

Eur J Clin Pharmacol

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Felodipine (0.075 mg/kg p.o.), a calcium antagonist, was given to 9 male volunteers, with and without indomethacin pretreatment. Diuresis and natriuresis occurred after felodipine without significant change in effective renal plasma flow or glomerular filtration rate. There was no significant change in urinary 6 keto PGF 1 alpha or urinary kallikrein excretion and indomethacin did not inhibit the natriuretic or diuretic response to felodipine. The felodipine induced diuresis and natriuresis appears most likely to be mediated by an action of the drug on renal tubules.

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The effect of two different calcium antagonists on the glomerular haemodynamics in the dog

Heller

Horáček

1990

Pflugers Arch.

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Kidney function of beagles fed a constant amount of food containing 3 mmol sodium.kgbodywt-1.day-1, and anaesthetized with pentobarbitone was investigated by clearance and micropuncture techniques during an intrarenal infusion of saline or the calcium antagonists verapamil (VER, 4 micrograms.kgbodywt-1.min-1) or nifedipine (NIF, 0.3 microgram.kgbodywt-1.min-1). Neither drug changed the mean arterial pressure. Apart from the natriuresis and diuresis, which were significantly greater with NIF than with VER, the response to both drugs was similar. Increases in renal blood flow (RBF; 17% with VER, 20% with NIF), glomerular filtration rate (GFR; VER: 34%; NIF: 39%) and filtration fraction (VER: 12%; NIF: 14%) were observed; similar values were obtained at the single nephron level. Pressure in glomerular capillaries, measured directly after ablation of a thin layer of cortex corticis, was increased by 11% with VER and 10% with NIF; no changes in proximal tubular and peritubular capillary pressure were seen. The glomerular ultrafiltration coefficient (Kf) did not change with either drug. Total arteriolar resistance was decreased (VER: 20%; NIF: 15%) due to a decrease in afferent resistance (VER: 31%; NIF: 27%) with no corresponding change in efferent resistance. The cause of the lack of responsiveness of the efferent arteriole remains unclear. In conclusion, in acute experiments with intrarenal administration, both drugs increase RBF and GFR by a preferential afferent dilatory mechanism without any change in Kf.

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Effect of Felodipine on Renal Hemodynamics and Excretion in the Dog

Cited by 5 publications

References 0 publications

Metoclopramide stimulates kaliuresis during felodipine without affecting its natriuresis.

Metoclopramide stimulates kaliuresis during felodipine without affecting its natriuresis.

The acute renal haemodynamic and endocrine response to felodipine in normal man

The effect of two different calcium antagonists on the glomerular haemodynamics in the dog

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