Angiotensin Converting Enzyme Inhibition Does Not Prevent the Natriuretic Effect of Felodipine

Hamersvelt, Henk W. van; Wetzels, Jack F.M.; Kloke, H. J.; Koene, R. A. P.; Huysmans, F. T. M.

doi:10.1097/00005344-199303000-00018

Cited by 4 publications

(5 citation statements)

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“…The combination of ACE inhibitor plus calcium antagonist has been studied less extensively than ACE inhibitor/diuretic combinations, with many of the studies using a dihydropyridine calcium antagonist (nifedipine, felodipine, amlodipine or isradipine) 34–37 . Only a few studies have investigated the calcium antagonists verapamil 48 , 49 and diltiazem 50 incombination with ACE inhibitors as first‐ and second‐line treatment.…”

Section: Ace Inhibitor and Diuretic Combinationsmentioning

confidence: 99%

“…Since ACE inhibitors result in va'iodilation, a more balanced arteriolar and venous dilation might result from dual-acting vasodilatortreatment. Volunteer studies have shown that the natriuretic effct<; of felodipine are unchanged during concurrent administn1tion of ramipril, 35 but the reflex tachycardia a<;sociated with the calcium antaonist is blunted. 36 In a further volunteer study, it was reported that a ramipril-felodipine combination had a greater protective effect against the untoward renal response to physical stress than either drug alone.…”

Section: Rationalementioning

confidence: 99%

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Fixed Dose Combinations of Ace Inhibitors

Rangoonwala¹,

Schulz²,

Bauer³

1996

Int J Clinical Practice

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SUMMARY First‐line antihypertensive monotherapy is effective in reducing blood pressure to within the normal range in approximately 50% of patients. Normalisation in the remaining patients may require a combination of two or more drugs. This review considers the clinical efficacy and tolerability of combinations involving angiotensin‐converting enzyme (ACE) inhibitors. The efficacy of combinations with diuretics or calcium antagonists, as initial therapy or in patients with inadequate responses to monotherapy, has been demonstrated in many trials. With combination therapy, normalisation rates approaching 80% can be achieved using submaximal doses of both components. Therapy with both combinations is well tolerated; with ACE inhibitors reducing the diuretic metabolic effects or counteracting some calcium antagonist‐associated vasodilatory effects. Data on ACE inhibitors with beta‐blockers are limited. When patients respond inadequately to first‐line monotherapy, the increasing availability of drug combinations will allow individual selection of the most appropriate combination, taking account of additional risk factors and concomitant disease.

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Section: Ace Inhibitor and Diuretic Combinationsmentioning

confidence: 99%

Section: Rationalementioning

confidence: 99%

Fixed Dose Combinations of Ace Inhibitors

Rangoonwala¹,

Schulz²,

Bauer³

1996

Int J Clinical Practice

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“…1 These drugs have short-term diuretic and natriuretic effects, 2 which may contribute to their antihypertensive action. Clearance studies in humans 3 …”

Section: Metoclopramide Stimulates Kaliuresis During Felodipine Withomentioning

confidence: 99%

“…During metoclopramide and dextrose, two 30-minute urine collections were made before felodipine or solvent was started in order to study the effect of pretreatment. Based on earlier studies, 3 we used a felodipine infusion schedule aiming at stable, subtherapeutic levels for the first 90 minutes (low dose) and therapeutic levels 23 for the last 90 minutes (therapeutic dose). To reach this, 0.10 ftg/kg per minute of felodipine (Plendil) was infused for the first 30 minutes, followed by 0.04 jig/kg P e r minute for the next 60 minutes (cumulative dose, 0.39±0.04 mg in 90 minutes, mean±SD).…”

Section: Study Protocolmentioning

confidence: 99%

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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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