Influence of nicardipine on renal hemodynamics and segmental tubular reabsorption of sodium in humans.
Calcium antagonists induced natriuresis in humans as well as in experimental animals. However, the tubular sites involved have not been precisely evaluated in humans. Using both free-water and lithium clearance, the latter as a marker of absolute sodium distal delivery, we measured segmental tubular movement of sodium before and after acute intravenous (i.v.) nicardipine administration 2.5 mg as a single dose in eight healthy normotensive volunteers on normal sodium diet. Nicardipine decreased slightly but significantly the mean arterial pressure (MAP) (from 98.9 +/- 8.8 to 91.8 +/- 9.2 mm Hg; p less than 0.01) and the renal vascular resistance (from 6,142 +/- 1,082 to 5,578 +/- 893 dynes.s/cm5 . 1.73 m2; p less than 0.05), whereas the glomerular filtration rate (GFR), the renal plasma flow (RPF), and the filtration fraction (FF) were unchanged. Nicardipine acutely increased the absolute and the fractional excretion of sodium (from 282 +/- 60 to 427 +/- 152 mumol/min.1.73 m2; p less than 0.01 and from 0.015 +/- 0.004 to 0.023 +/- 0.013; p less than 0.01, respectively). When assessed by either lithium clearance or free-water clearance, both proximal and distal fractional reabsorption of sodium were decreased by nicardipine. These results indicate that the nicardipine-induced natriuretic effect is due to decreased sodium reabsorption in both proximal and distal sites of the nephron. Shifts in segmental tubular sodium reabsorption obtained from either free-water or lithium clearance were directionally similar but quantitatively different.
Hannedouche
T
T
Department of Nephrology, Necker Hospital, Paris, France.
Delgado
A
A
Gnionsahé
A
A
Lacour
B
B
Grunfeld
J P
JP
D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D005260:Female; D006801:Humans; D007684:Kidney Tubules / Q000187:drug effects / Q000378:metabolism*; D008094:Lithium / Q000378:metabolism; D008297:Male; D009318:Natriuresis / Q000187:drug effects; D009529:Nicardipine / Q000494:pharmacology*; D010710:Phosphates / Q000378:metabolism; D012079:Renal Circulation / Q000187:drug effects*; D012964:Sodium / Q000378:metabolism*; D014527:Uric Acid / Q000652:urine
D010710:Phosphates; D014527:Uric Acid; D008094:Lithium; D012964:Sodium; D009529:Nicardipine