Differential effects of endothelin on activation of renal mechanosensory nerves: stimulatory in high-sodium diet and inhibitory in low-sodium diet.
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 (ETBR)-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 ETBR 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 ETAR 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 ETAR antagonist to ETBR-blocked renal pelvises restored the responsiveness of renal sensory nerves in rats fed a high-sodium diet. Adding the ETBR antagonist to ETAR-blocked pelvises suppressed the responsiveness of the renal sensory nerves in rats fed a low-sodium diet. In conclusion, activation of ETBR and ETAR 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 ETBR-deficient rat.
Kopp
Ulla C
UC
Dept. of Internal Medicine, VA Medical Center, University of Iowa Carver College of Medicine, Bldg. 3, Rm. 226, Highway 6W, Iowa City, IA 52246, USA. ulla-kopp@uiowa.edu
Cicha
Michael Z
MZ
Smith
Lori A
LA
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D004039:Diet, Sodium-Restricted; D065130:Endothelin A Receptor Antagonists; D065131:Endothelin B Receptor Antagonists; D016232:Endothelins / Q000235:genetics / Q000502:physiology*; D005727:Ganglia, Spinal / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D006973:Hypertension / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D007668:Kidney / Q000294:innervation* / Q000378:metabolism; D008297:Male; D040542:Mechanotransduction, Cellular / Q000187:drug effects / Q000502:physiology*; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism*; D009842:Oligopeptides / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044022:Receptor, Endothelin A / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D044023:Receptor, Endothelin B / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D012982:Sodium, Dietary / Q000494:pharmacology*; D013373:Substance P / Q000378:metabolism
D000959:Antihypertensive Agents; D065130:Endothelin A Receptor Antagonists; D065131:Endothelin B Receptor Antagonists; D016232:Endothelins; D009842:Oligopeptides; D010456:Peptides, Cyclic; D010880:Piperidines; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D012982:Sodium, Dietary; D013373:Substance P; C086539:BQ 788; C072247:cyclo(Trp-Asp-Pro-Val-Leu)