URIDINE KINASE INHIBITION IS INVOLVED IN THE VASODILATOR EFFECTS OF MINOXIDIL IN THE RAT

Abstract

1. Since minoxidil is a pyrimidine derivative, its actions on vascular smooth muscle may derive from structural relationships to the uridine nucleotides, which have been shown to be vasoconstrictive in the rat. 2. Minoxidil at a low vasodepressor dose of 0.03 mg/kg per min abolished the pressor response to uridine at doses from 2 to 8 mumol/kg per min, but did not reduce the responses to uridine monophosphate or uridine diphosphate in similar pressor doses, suggesting an action on either transport of uridine into cells or on uridine kinase which catalyses phosphorylation of uridine to uridine monophosphate, the mediator of uridine's vascular actions. 3. The active metabolite of minoxidil was found to inhibit rat liver uridine kinase in vivo using an HPLC technique. 4. Plasma uridine concentration was significantly higher in 11 hypertensive patients on minoxidil compared with pretreatment values, suggesting that uridine kinase inhibition is of a degree sufficient to increase the circulating pool of uridine. 5. The data is consistent with uridine kinase inhibition being a mechanism for the vasodilator actions of minoxidil.