Endothelin mediates phospholipase C stimulation in the proximal tubule during initiation of compensatory renal growth in adult rats.

AIM

Mechanisms that initiate compensatory renal growth following unilateral nephrectomy are incompletely understood. An early event following unilateral nephrectomy is the activation of phospholipase C in the apical membrane of the proximal tubule, mediated by an unknown agonist. We tested the hypothesis that endothelin is responsible for the stimulation of phospholipase C in rat proximal tubule following unilateral nephrectomy.

METHODS

Compensatory renal growth was induced in adult male rats by unilateral nephrectomy. 1,2-Diacylglycerol, a product of phospholipase C activation, was measured in renal cortical slices and isolated proximal tubules, respectively, 20 min following unilateral nephrectomy, or after incubation of the slices or proximal tubules with plasma from unilaterally nephrectomized or sham-operated rats.

RESULTS

Twenty min following unilateral nephrectomy, an increase in 1,2-diacylglycerol concentration occurred in the renal cortex. Bosentan, a nonselective endothelin receptor antagonist, as well as an anti-endothelin-1 antibody administered intravenously, completely inhibited this 1,2-diacylglycerol accumulation in renal cortex. Incubation of renal cortical slices with plasma from unilaterally nephrectomized or bilaterally nephrectomized rats, stimulated 1,2-diacylglycerol production in isolated proximal tubule apical membranes. Again, bosentan prevented the increase evoked by incubation with plasma from unilaterally nephrectomized rats. Finally, concentration of endothelin-1 increased in renal cortex in response to unilateral nephrectomy.

CONCLUSION

These results make evident the role of endothelin in stimulation of phospholipase C in proximal tubule following unilateral nephrectomy, suggesting participation of the endothelin system during the initiation of the compensatory renal growth.