In vitro inhibition of rho-aminohippurate transport by halogenated anesthetics

The effects of four commonly used halogenated anesthetic agents (methoxyflurane, halothane, enflurane and fluroxene) on rho-aminohippurate (PAH) uptake by rabbit renal cortical slices were examined. All agents depressed PAH uptake in a linear dose-dependent manner after 60 minutes of incubation and the effect was reversible. When the data were normalized for anesthetic potency, all agents exhibited a parallel dose-response curve. Since these agents do not share a common metabolite, it is concluded that the depression of PAH transport is mediated primarily by a direct effect of the agents acting through a common pathway. Exposure of kidney slices to perithreshold concentrations of halothane and enflurane for 180 minutes did not result in a cumulative inhibitory effect on PAH transport. A slight time-dependent effect was seen with methoxyflurane. It is suggested that with prolonged exposure metabolic conversion of methoxyflurane may occur leading to further inhibition of PAH uptake.