Model explaining the relation between distal nephron Li+ reabsorption and urinary Na+ excretion in rats.
Li+ may be reabsorbed via an amiloride-sensitive mechanism in the collecting ducts of rats administered a low-Na+ diet. This was investigated by measuring the increase in fractional urinary excretion of Li+ (FELi) in response to amiloride in conscious rats at two different levels of plasma Li+ concentration and after administration of bendroflumethiazide (BFTZ), angiotensin III (ANG III), and aldosterone (Aldo). The results confirmed that amiloride increased (FELi) in rats on a low-Na+ diet (20 +/- 1 to 35 +/- 1%, means +/- SE), whereas no increase was observed in rats on a normal Na+ diet (37 +/- 1 to 38 +/- 1%). The lithiuretic effect of amiloride was 1) abolished by preadministration of BFTZ (32 +/- 1 to 33 +/- 2%) to Na(+)-deprived rats and 2) increased by ANG III (27 +/- 3 to 33 +/- 2%) and Aldo (25 +/- 2 to 37 +/- 2%) in Na(+)-replete rats. Amiloride-induced changes in FELi were independent of plasma Li+ concentration but inversely related to the fractional excretion of Na+ and the amiloride-sensitive excretion of K+. These results are compatible with the hypothesis that a low tubular Na+ concentration reduces end-tubular Na+ reabsorption and results in hyperpolarization of the apical membrane, thus favoring Li+ uptake into the cells.
Shalmi
M
M
Department of Pharmacology, University of Copenhagen, Denmark.
Jonassen
T
T
Thomsen
K
K
Kibble
J D
JD
Bie
P
P
Christensen
S
S
D000450:Aldosterone / Q000494:pharmacology; D000584:Amiloride / Q000494:pharmacology; D000805:Angiotensin III / Q000494:pharmacology; D000818:Animals; D001539:Bendroflumethiazide / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D007684:Kidney Tubules / Q000378:metabolism; D008094:Lithium / Q000378:metabolism*; D009318:Natriuresis / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000378:metabolism*
D000805:Angiotensin III; D000450:Aldosterone; D001539:Bendroflumethiazide; D000584:Amiloride; D008094:Lithium; D012964:Sodium