title: Bosentan normalizes the GFR response to renal nerve stimulation following reversible unilateral ureteric obstruction in the rat.
abstract: We investigated the renal response to direct renal nerve stimulation, 2 weeks following reversal of 24-h unilateral (left) ureteric obstruction. Renal nerve stimulation caused a 13-15 % fall in renal blood flow, in 4 groups of anesthetized rats following ureteric obstruction (n=9) or a sham operation (n=7) both with (n=9) and without (n=7) treatment with the mixed ET(A/B) receptor antagonist, bosentan. In the sham-operated rats, renal nerve stimulation did not change glomerular filtration rate but reduced urine flow rate (37+/-3 %, P<0.001), and absolute (38+/-4 %, P<0.001) and fractional (35+/-5 %, P<0.01) sodium excretion. Following unilateral ureteric obstruction, renal nerve stimulation increased glomerular filtration rate by 22+/-3 % (P<0.01), but reduced urine flow rate (14+/-2 %, P<0.001) and fractional sodium excretion (23+/-5 %, P<0.01). Bosentan treatment had no effect on baseline or renal responses to renal nerve stimulation in the sham group but normalized the renal response to renal nerve stimulation in the unilateral ureteric obstruction group. We conclude that 14 days after a 24-h period of unilateral ureteric obstruction there is an increase in GFR in response to direct renal nerve stimulation, which is due, in part, to the actions of endothelin at the time of obstruction.
authors.affiliation: Department of Physiology, Otago School of Medical Sciences, University of Otago, Dunedin, New Zealand. ged.davis@otago.ac.nz.
authors.forename: F T
authors.initials: FT
authors.lastname: Hammad
authors.forename: A M
authors.initials: AM
authors.lastname: Wheatley
authors.forename: G
authors.initials: G
authors.lastname: Davis
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D000077300:Bosentan; D004558:Electric Stimulation; D065128:Endothelin Receptor Antagonists / Q000494:pharmacology; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D007668:Kidney / Q000187:drug effects / Q000294:innervation / Q000503:physiopathology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012079:Renal Circulation / Q000187:drug effects; D013449:Sulfonamides / Q000494:pharmacology*; D013564:Sympathetic Nervous System / Q000187:drug effects; D014517:Ureteral Obstruction / Q000503:physiopathology*
chemical_list: D000959:Antihypertensive Agents; D065128:Endothelin Receptor Antagonists; D013449:Sulfonamides; D000077300:Bosentan