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Renin release from isolated juxtaglomerular apparatus depends on macula densa chloride transport
J N Lorenz1, H Weihprecht, J Schnermann
1Department of Physiology, University of Michigan, Ann Arbor 48109.
Insights
Renin secretion is stimulated by transport blockers and inhibited by chloride, not sodium, at the macula densa. This supports the Na-K-2Cl cotransporter
Area of Science:
- Nephrology
- Renal Physiology
- Molecular Biology
Background:
- The juxtaglomerular apparatus plays a crucial role in regulating blood pressure through renin secretion.
- Macula densa cells within the juxtaglomerular apparatus sense changes in tubular fluid composition to modulate renin release.
- The precise ionic mechanisms underlying macula densa-mediated renin secretion remain incompletely understood.
Purpose of the Study:
- To investigate the role of ion transport, specifically involving sodium and chloride, in macula densa-mediated renin secretion.
- To determine whether inhibition of the Na-K-2Cl cotransporter influences renin secretion.
- To elucidate the specific ion (Na+ or Cl-) responsible for the macula densa's control of renin release.
Main Methods:
- Utilized isolated, perfused, and superfused rabbit juxtaglomerular apparatus preparations.
- Administered transport inhibitors, such as bumetanide, to tubular and bath compartments.
- Performed ion substitution studies by altering luminal concentrations of sodium and chloride salts.
Main Results:
- Luminal perfusion with bumetanide significantly increased renin secretion, while bath application had no effect.
- Increased luminal chloride concentration inhibited renin secretion, whereas increased sodium concentration did not.
- High NaCl perfusion, used as a positive control, effectively decreased renin secretion.
Conclusions:
- Renin secretion is directly stimulated by luminal transport blockers acting on the macula densa.
- Macula densa-mediated renin secretion is inhibited by increased luminal chloride but not sodium concentrations.
- These findings support the hypothesis that the Na-K-2Cl cotransporter is the initiating signal for macula densa control of renin secretion.
Abstract:
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.