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 (NO) and endothelium derived hyperpolarising factor (EDHF) to the endothelium dependent, acetylcholine induced vasodilatation in isolated perfused rat kidney.

METHODS

The renal response to acetylcholine was compared in phenylephrine preconstricted renal vasculature under basal conditions and after the infusion of N omega-nitro-L-arginine (L-NAME), an inhibitor of NO synthesis, and tetraethylammonium, a non-specific blocker of potassium channels that inhibits acetylcholine induced hyperpolarisation. These inhibitors were given alone and together. In another experiment, the renal response to acetylcholine was compared when the vasculature was preconstricted with phenylephrine or with 40 and 80 mM KCl under basal conditions and after the infusion of L-NAME. All experiments were done in the presence of indomethacin.

RESULTS

Inhibition of NO generation with L-NAME reduced the vasodilator responses to acetylcholine by approximately 50%, and enhanced the response to sodium nitroprusside in the isolated perfused kidney preconstricted with phenylephrine. Infusion of tetraethylammonium also decreased the response to acetylcholine by approximately 50% and increased vasodilatation responses to sodium nitroprusside. The simultaneous administration of both inhibitors (L-NAME and tetraethylammonium) had a summational effect which almost completely suppressed acetylcholine induced vasodilatation. Increasing concentrations of extracellular potassium produced a dose related decrease in acetylcholine induced vasodilatation. These attenuated responses were almost abolished after the infusion of L-NAME.

CONCLUSIONS

Our results suggest that the vasodilator response to acetylcholine in isolated perfused rat kidneys is subserved by EDHF and nitric oxide, both endothelium derived mediators participating to a similar extent.