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WATER AND ELECTROLYTE HOMEOSTASIS

Differential effects of endothelin on activation of renal mechanosensory nerves: stimulatory in high-sodium diet and inhibitory in low-sodium diet

Department of Internal Medicine, Department of Veterans Affairs Medical Center, University of Iowa Carver College of Medicine, Iowa City, Iowa

Submitted 14 December 2005 ; accepted in final form 2 June 2006

Activation of renal mechanosensory nerves is enhanced by high and suppressed by low sodium dietary intake. Afferent renal denervation results in salt-sensitive hypertension, suggesting that activation of the afferent renal nerves contributes to water and sodium balance. Another model of salt-sensitive hypertension is the endothelin B receptor (ET_BR)-deficient rat. ET and its receptors are present in sensory nerves. Therefore, we examined whether ET receptor blockade altered the responsiveness of the renal sensory nerves. In anesthetized rats fed high-sodium diet, renal pelvic administration of the ET_BR antagonist BQ-788 reduced the afferent renal nerve activity (ARNA) response to increasing renal pelvic pressure 7.5 mmHg from 26 ± 3 to 9 ± 3% and the PGE₂-mediated renal pelvic release of substance P from 9 ± 1 to 3 ± 1 pg/min. Conversely, in rats fed low-sodium diet, renal pelvic administration of the ET_AR antagonist BQ-123 enhanced the ARNA response to increased renal pelvic pressure from 9 ± 2 to 23 ± 6% and the PGE₂-mediated renal pelvic release of substance P from 0 ± 0 to 6 ± 1 pg/min. Adding the ET_AR antagonist to ET_BR-blocked renal pelvises restored the responsiveness of renal sensory nerves in rats fed a high-sodium diet. Adding the ET_BR antagonist to ET_AR-blocked pelvises suppressed the responsiveness of the renal sensory nerves in rats fed a low-sodium diet. In conclusion, activation of ET_BR and ET_AR contributes to the enhanced and suppressed responsiveness of renal sensory nerves in conditions of high- and low-sodium dietary intake, respectively. Impaired renorenal reflexes may contribute to the salt-sensitive hypertension in the ET_BR-deficient rat.

endothelin B receptor; endothelin A receptor; substance P; prostaglandin E₂