CONTRIBUTION OF ENDOTHELIUM-DERIVED RELAXING FACTORS TO ACETYLCHOLINE-INDUCED VASODILATATION IN THE RAT-KIDNEY

Objective: The aim was to evaluate the contribution of nitric oxide (N O) and endothelium derived hyperpolarising factor (EDHF) to the endoth elium dependent, acetylcholine induced vasodilatation in isolated perf used rat kidney. Methods: The renal response to acetylcholine was comp ared in phenylephrine preconstricted renal vasculature under basal con ditions and after the infusion of N-omega-nitro-L-arginine (L-NAME), a n inhibitor of NO synthesis. and tetraethylammonium, a non-specific bl ocker of potassium channels that inhibits acetylcholine induced hyperp olarisation. These inhibitors were given alone and together. In anothe r experiment, the renal response to acetylcholine was compared when th e vasculature was preconstricted with phenylephrine or with 40 and 80 mM KCl under basal conditions and after the infusion of L-NAME. All ex periments were done in the presence of indomethacin. Results: Inhibiti on of NO generation with L-NAME reduced the vasodilator responses to a cetylcholine by similar to 50%, and enhanced the response to sodium ni troprusside in the isolated perfused kidney preconstricted with phenyl ephrine. Infusion of tetraethylammonium also decreased the response to acetylcholine by similar to 50% and increased vasodilatation response s to sodium nitroprusside. The simultaneous administration of both inh ibitors (L-NAME and tetraethylammonium) had a summational effect which almost completely suppressed acetylcholine induced vasodilatation. In creasing concentrations of extracellular potassium produced a dose rel ated decrease in acetylcholine induced vasodilatation. These attenuate d responses were almost abolished after the infusion of L-NAME. Conclu sions: Our results suggest that the vasodilator response to acetylchol ine in isolated perfused rat kidneys is subserved by EDHF and nitric o xide, both endothelium derived mediators participating to a similar ex tent.