Effects of Felodipine on the dog kidney: a lithium clearance study.
This study was performed in order to investigate the possible influence of sympathetic nerve activity on the effects of the dihydropyridine calcium antagonist felodipine on absolute and fractional reabsorption rates of sodium and water in proximal and distal tubular segments in the dog kidney. Clearance of 51Cr-EDTA was used as a measure of glomerular filtration rate (GFR). GFR, urinary excretion rates of sodium and water, and lithium clearance (C-Li) were used for assessing the absolute and fractional tubular reabsorption rates. Felodipine infusion into the right renal artery increased renal vascular conductance (renal blood flow divided by renal arteriovenous pressure gradient) significantly (by 9%) while GFR remained unchanged. Calculated absolute proximal reabsorption rates remained unchanged while distal sodium reabsorption rate increased significantly from 2.1 +/- 0.3 to 2.7 +/- 0.4 mmol min-1. Sodium clearance (C-Na) increased from 0.22 +/- 0.08 to 0.40 +/- 0.07 ml min-1. The alpha-adrenergic blockade with phentolamine did not affect renal haemodynamic or excretory variables, nor did it influence the haemodynamic response to felodipine. After alpha-adrenergic blockade felodipine caused an increase in C-Na from 0.28 +/- 0.06 ml min-1 to 0.63 +/- 0.04 ml min-1, which was significantly greater than that measured after felodipine alone. The distal load (C-Li) was not significantly different from that obtained after felodipine alone, but distal sodium reabsorption rate increased less significantly after alpha-adrenergic blockade. The results suggest that felodipine, by its effect on tubular flow and/or composition, activates local alpha-adrenergic reflex mechanism(s), which stimulates distal sodium reabsorption, thereby attenuating the natriuretic effect.
Abildgaard
U
U
Department of Cardiology, Gentofte University Hospital, Copenhagen, Denmark.
Daugaard
G
G
Leyssac
P P
PP
Amtorp
O
O
D000042:Absorption; D000818:Animals; D004285:Dogs; D015736:Felodipine / Q000494:pharmacology*; D005260:Female; D005919:Glomerular Filtration Rate; D007668:Kidney / Q000098:blood supply / Q000187:drug effects / Q000502:physiology*; D007684:Kidney Tubules / Q000378:metabolism; D007700:Kinetics; D008094:Lithium / Q000378:metabolism*; D008297:Male; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology; D012079:Renal Circulation / Q000187:drug effects; D012964:Sodium / Q000378:metabolism
D011942:Receptors, Adrenergic, alpha; D008094:Lithium; D012964:Sodium; D015736:Felodipine