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(Hypertension. 2007;49:141.)
© 2007 American Heart Association, Inc.

Original Articles

Activation of Endothelin-A Receptors Contributes to Angiotensin-Induced Suppression of Renal Sensory Nerve Activation

From the Departments of Internal Medicine and Pharmacology, Department of Veterans Affairs Medical Center and University of Iowa Carver College of Medicine, Iowa City.

Correspondence to Ulla C. Kopp, Department of Internal Medicine, VA Medical Center, Building 3, Room 226, Highway 6W, Iowa City, IA 52246. E-mail ulla-kopp{at}uiowa.edu

Activation of renal mechanosensory nerves is enhanced by a high-sodium diet and suppressed by a low-sodium diet. Angiotensin (Ang) II and endothelin (ET)-1 each contributes to the impaired responsiveness of renal mechanosensory nerves in a low-sodium diet. We examined whether stimulation of ETA receptors (Rs) contributes to Ang II-induced suppression of the responsiveness of renal mechanosensory nerves. In anesthetized rats fed a low-sodium diet, renal pelvic administration of the Ang type I receptor (AT1-R) antagonist losartan enhanced the afferent renal nerve activity (ARNA) response to increasing renal pelvic pressure 7.5 mm Hg from 7±2% to 15±2% and the prostaglandin (PG) E₂–mediated substance P release from 0±1 to 8±1 pg/min. Adding the ETA-R antagonist BQ123 to the renal pelvic perfusate containing losartan did not produce any further enhancement of the ARNA response or PGE₂-mediated release of substance P (17±3% and 8±1 pg/min). Likewise, renal pelvic administration of BQ123 and BQ123+losartan resulted in similar enhancements of the ARNA responses to increased renal pelvic pressure and PGE₂-mediated substance P release. In high-sodium-diet rats, pelvic administration of Ang II reduced the ARNA response to increased renal pelvic pressure from 27±4% to 8±3% and the PGE₂-mediated substance P release from 9±0 to 1±1 pg/min. Adding BQ123 to the renal pelvic perfusate containing Ang II restored the increases in ARNA and the PGE₂-mediated substance P release toward control (27±6% and 7±1 pg/min). In conclusion, stimulation of ETA-R plays an important contributory role to the Ang II-mediated suppression of the activation of renal mechanosensory nerves in conditions of low-sodium diet.

Key Words: ETA-receptors • AT1-receptors • afferent renal nerves • PGE₂ • substance P • BQ123 • losartan