Dopaminergic modulation of acute renal effects of nicardipine.
In order to investigate whether dopamine receptors are involved in the acute natriuretic effects of calcium channel blockade, experiments were carried out in humans with uncomplicated essential hypertension. In 8 hypertensives 5 mg intravenous nicardipine produced a large decrease in blood pressure and renal vascular resistance, a slight but significant increase in glomerular filtration rate (GFR) and marked natriuresis. When a second identical experiment was performed in the same subjects with the addition of 10 mg metoclopramide as dopamine blocker, changes in sodium excretion and vascular resistance were the same, but GFR did not increase during nicardipine. In a second set of experiments (n = 5) the same design was used, but nicardipine was infused at a dose of 0.01 mg/kg, ie, seven times less than in previous experiments. Under these conditions, blood pressure, renal vascular resistance and GFR did not change, but significant natriuresis occurred. Natriuresis was almost completely prevented by metoclopramide. In 5 additional hypertensives, metoclopramide alone was infused and 0.01 mg/kg nicardipine was added to the infusion. No change in any parameter was observed. Our findings suggest that the dopaminergic system participates in maintaining or increasing GFR during blood pressure reduction by calcium antagonists, although renal vasodilation and natriuresis are largely independent of dopamine receptor activity. In addition, when low doses of calcium antagonists produce natriuresis in the absence of renal or systemic hemodynamic changes (direct tubular effect), dopamine blockade is able to blunt this effect. This indicates a modulation by dopaminergic receptors of the direct tubular action of calcium antagonists.
Montanari
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A
Istituto di Semeiotica Medica, Università di Parma, Italy.
Ragni
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G
Vallisa
D
D
Colla
R
R
Serventi
M
M
Novarini
A
A
Coruzzi
P
P
D001794:Blood Pressure / Q000187:drug effects; D004298:Dopamine / Q000502:physiology*; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000503:physiopathology; D007668:Kidney / Q000187:drug effects*; D008297:Male; D008787:Metoclopramide / Q000494:pharmacology; D008875:Middle Aged; D009529:Nicardipine / Q000494:pharmacology*; D013997:Time Factors
D009529:Nicardipine; D008787:Metoclopramide; D004298:Dopamine