The renal functional responses to 5-HT1A receptor agonist, flesinoxan, in anaesthetized, normotensive rat.
1. The present study was designed to examine the effects of a centrally acting 5-HT1A receptor agonist, flesinoxan, on the cardiovascular system and renal haemodynamics and excretory function. 2. In chloralose-urethane anaesthetized Wistar rats, i.v. administration of bolus doses of flesinoxan, at 30, 100, 300 and 1000 micrograms kg-1, caused significant, dose-dependent decreases in mean arterial pressure, of 33 +/- 2 mmHg (P < 0.001) and heart rate of 57 +/- 9 beats min-1 (P < 0.001) at the highest dose used. Despite this substantial fall in perfusion pressure there were no meaningful changes in the renal excretion of water and sodium. In a second group of rats, reduction of renal perfusion pressure mechanically to the same values as observed in rats given flesinoxan (i.e. 100, 92, 84 and 76 mmHg) produced reductions in urine flow, absolute and fractional sodium excretions reaching a maximum of 74, 86 and 84% respectively (all P < 0.001) at the lowest pressure. These reductions were significantly larger than those seen in the previous group of animals. 3. In the group of rats subjected to renal denervation, flesinoxan produced changes in blood pressure and heart rate which were not different from those observed in intact animals. However, the reduction in pressure was accompanied by significant decreases in urine flow of 71%, absolute sodium excretion of 68% and fractional sodium excretion of 67% (all P < 0.001) at the highest dose, which were all significantly greater than the changes seen in the innervated animals but were not different from those observed when renal perfusion pressure was reduced mechanically. 4. The findings of this investigation showed that flesinoxan was effective in lowering blood pressure and heart rate in the anaesthetized rat, which was probably due to decreased sympathetic nerve activity.Renal excretion of water and sodium was well preserved in the face of the flesinoxan-induced hypotension.The maintenance of fluid excretion with flesinoxan appeared to be mediated via changes in renal nerve activity, since it did not occur when the kidney was denervated.
Department of Physiology, Medical School, Birmingham.
A L
AL
Chamienia
E J
EJ
Johns
D000758:Anesthesia; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003714:Denervation; D004573:Electrolytes / Q000097:blood / Q000652:urine; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D007668:Kidney / Q000187:drug effects* / Q000294:innervation; D008297:Male; D009318:Natriuresis / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012079:Renal Circulation / Q000187:drug effects; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*
D004573:Electrolytes; D010879:Piperazines; D017366:Serotonin Receptor Agonists; C056895:flesinoxan