Vancomycin-Resistant Lactococcus lactis 1A-1 Isolated from a Competitive Exclusion Product Transfers Vancomycin Resistance Genes to Staphylococcus aureus

Abstract

Prazosin, a structurally and mechanistically novel antihypertensive agent, is the culmination of a systematic synthesis and pharmacologic developmental effort which had as its goal the development of an agent that would lower blood pressure by direct vasodilation. Pharmacologic studies have demonstrated that the vasodilator action of prazosin is confined primarily to the arterioles and that antihypertensive effects are unaccompanied by excessive increases in heart rate. Evidence is presented rationalizing these observations on a biochemical basis. Results of inhibitory studies with isolated cyclic nucleotide phosphodiesterases are consistent with the hypothesis that prazosin elicits its therapeutic effects by increasing intracellular levels of cyclic AMP at vascular sites and intracellular levels of cyclic GMP at cholinergic receptor sites in the heart. Tissue distribution studies with radioactive prazosin-2-14C are in accord with this rationale and further support the mechanistic conclusions reached on the basis of pharmacologic observations. Pharmacokinetic and biotransformation studies indicate that prazosin is well absorbed and is excreted principally in metabolized form with biliary excretion being the major route of elimination. A high margin of safety for prazosin has been established in safety evaluation studies in a variety of animal species.