title: Activation of endothelin-a receptors contributes to angiotensin-induced suppression of renal sensory nerve activation.
abstract: 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) E(2)-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 PGE(2)-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 PGE(2)-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 PGE(2)-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 PGE(2)-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.
authors.affiliation: Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, USA. ulla-kopp@uiowa.edu
authors.forename: Ulla C
authors.initials: UC
authors.lastname: Kopp
authors.forename: Michael Z
authors.initials: MZ
authors.lastname: Cicha
authors.forename: Lori A
authors.initials: LA
authors.lastname: Smith
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology / Q000502:physiology*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D015232:Dinoprostone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D065130:Endothelin A Receptor Antagonists; D007668:Kidney / Q000294:innervation*; D007682:Kidney Pelvis / Q000187:drug effects / Q000378:metabolism; D019808:Losartan / Q000494:pharmacology; D008297:Male; D008465:Mechanoreceptors / Q000187:drug effects / Q000502:physiology; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology*; D010456:Peptides, Cyclic / Q000494:pharmacology; D011312:Pressure; D051381:Rats; D017207:Rats, Sprague-Dawley; D044022:Receptor, Endothelin A / Q000502:physiology*; D012982:Sodium, Dietary / Q000008:administration & dosage / Q000494:pharmacology; D013373:Substance P / Q000378:metabolism
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D004338:Drug Combinations; D065130:Endothelin A Receptor Antagonists; D010456:Peptides, Cyclic; D044022:Receptor, Endothelin A; D012982:Sodium, Dietary; D000804:Angiotensin II; D013373:Substance P; D019808:Losartan; D015232:Dinoprostone; C072247:cyclo(Trp-Asp-Pro-Val-Leu)