Inhibition of eicosanoid formation by prazosin in the rabbit renal cortex

The influence of the oral administration of prazosin (an alpha 1-adrenergic blocker) and propranolol (a beta-adrenergic blocker) on eicosanoid formation in renal cortices and papillae was evaluated in rabbits maintained on a high cholesterol diet. Rabbit renal microsomal fractions were incubated with radiolabeled arachidonic acid (AA) and glutathione (GSH) and the levels of metabolites were determined by thin layer chromatography (TLC), autoradiography and reverse phase-high performance liquid chromatography (RP-HPLC). Rabbits on a high cholesterol diet showed no significant differences in total eicosanoid production compared to rabbits on a normal diet. Prazosin was found to significantly inhibit the formation of all eicosanoids in the renal cortex. In contrast, propranolol had no such inhibitory effect in the renal cortex. Neither drug had a significant effect on eicosanoid formation in the renal papilla. While oral administration of prazosin effectively inhibited the formation of all eicosanoids in the cortex, the addition of prazosin in vitro at physiological concentrations showed no such effect. These findings may have reflected alpha-receptor mediated event(s) which resulted in an alteration in eicosanoid formation in the kidney, suggesting an interaction between the sympathetic nervous system and the AA cascade.