Renal functional responses to the 5-HT1A receptor agonist flesinoxan: effects of controlled renal perfusion pressure.
The present study examined the effects of a centrally acting 5-HT1A receptor agonist flesinoxan on the renal sympathetic nerve control of the kidney while left renal perfusion pressure (RPP) was controlled at 80 mm Hg. In groups of chloralose/urethane-anesthetized Wistar rats, reduction in left kidney RPP significantly decreased the glomerular filtration rate (GFR), with much larger decreases in urine flow (UV) and absolute (UNaV) and fractional (FENa) sodium excretions, but raised systemic pressure as well as right kidney GFR and water and sodium excretion. In intact time-control rats, there were no time-dependent changes in left or right kidney GFR, UV, UNaV or FENa. Administration of bolus doses of flesinoxan at 30, 100 and 300 micrograms/kg i.v. in intact rats caused significant, dose-dependent decreases in mean systemic arterial pressure (23%) and heart rate (10%) (both P < .001). Although RPP was unchanged, there were significant increases in left kidney UV (118%), UNaV (385%) and FENa (277%) (all P < .005). Despite the substantial decrease in RPP at the right kidney, excretion of water and sodium was well preserved. In bilaterally renal-denervated rats, flesinoxan produced similar changes in blood pressure and heart rate but did not increase left kidney UV or sodium excretion, and the reduction in pressure caused significant decreases in right kidney UV, UNaV and FENa. These findings are consistent with the hypothesis that flesinoxan causes suppression of renal sympathetic tone, which leads to increased sodium and water excretion.
Chamienia
A L
AL
Department of Physiology, Medical School, Birmingham, UK.
Johns
E J
EJ
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D003714:Denervation; D004305:Dose-Response Relationship, Drug; D006439:Hemodynamics / Q000187:drug effects; D007668:Kidney / Q000187:drug effects* / Q000294:innervation / Q000502:physiology*; D008297:Male; D009318:Natriuresis / Q000187:drug effects; D010477:Perfusion; D010879:Piperazines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012079:Renal Circulation / Q000187:drug effects; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*
D000959:Antihypertensive Agents; D010879:Piperazines; D017366:Serotonin Receptor Agonists; C056895:flesinoxan