Renin release from isolated juxtaglomerular apparatus depends on macula densa chloride transport.
Transport inhibitor and ion substitution studies were performed using perfused, superfused preparations of the isolated rabbit juxtaglomerular apparatus to investigate transport dependency of macula densa-mediated renin secretion. In the first experimental series, tubular perfusion with a high-NaCl solution containing 10(-6) M bumetanide increased renin secretion compared with perfusion with high NaCl alone from 8.7 to 24.6 nano-Goldblatt hog units (nGU)/min. Bath addition of 10(-6) M bumetanide had no effect on renin release. The second series tested ability of luminal addition of 54 mmol/l Na or Cl salts to inhibit renin secretion, starting from a stimulated value produced by low-NaCl perfusion. Perfusion with a high-NaCl solution decreased renin secretion from 58.9 to 14.8 nGU/min, which served as a positive control. Addition of choline chloride decreased renin secretion from 42.7 to 16.6 nGU/min, and RbCl decreased renin secretion from 54.9 to 17.0 nGU/min. In contrast, addition of two different Na salts had no effect on renin release (from 41.7 to 31.6 nGU/min with sodium isethionate and from 14.1 to 13.5 nGU/min with sodium acetate). Also, in the presence of 26 mmol/l Cl, addition of 54 mmol/l Na had no effect on renin secretion (29.9-36.8 nGU/min). These data demonstrate that renin secretion is directly stimulated by luminal application of transport blockers and can be inhibited by increases in Cl concentration at the macula densa but not by changes in Na concentration. These results support the hypothesis that the initiating signal for macula densa control of renin secretion is an inverse change in transport rate via the luminal Na(+)-K(+)-2Cl- cotransporter.
Lorenz
J N
JN
Department of Physiology, University of Michigan, Ann Arbor 48109.
Weihprecht
H
H
Schnermann
J
J
Skøtt
O
O
Briggs
J P
JP
D000818:Animals; D001692:Biological Transport; D002034:Bumetanide / Q000494:pharmacology; D002352:Carrier Proteins / Q000378:metabolism; D002712:Chlorides / Q000378:metabolism* / Q000494:pharmacology; D002794:Choline / Q000494:pharmacology; D005260:Female; D007606:Juxtaglomerular Apparatus / Q000187:drug effects / Q000378:metabolism*; D007686:Kidney Tubules, Distal / Q000502:physiology*; D011817:Rabbits; D012083:Renin / Q000378:metabolism*; D012413:Rubidium / Q000494:pharmacology; D012965:Sodium Chloride / Q000494:pharmacology; D028021:Sodium-Potassium-Chloride Symporters
D002352:Carrier Proteins; D002712:Chlorides; D028021:Sodium-Potassium-Chloride Symporters; D002034:Bumetanide; D012965:Sodium Chloride; D012083:Renin; D012413:Rubidium; C032710:rubidium chloride; D002794:Choline