Is it possible to develop drugs that act more selectively on large arteries?

Background Patients with high pulse pressures have an increased risk for ca rdiovascular events, Drugs that selectively decrease high pulse pressure ma y be of interest for these patients. Such drugs have a more pronounced effe ct on large arteries than on resistance vessels, Objective To compare the selectivity to large arteries of the new nitric ox ide donor sinitrodil with the classic nitrate isosorbide dinitrate in healt hy young men in order to investigate whether it is possible to develop drug s that act more selectively on large arteries. Design The study had a double-blind, 5-way cross-over design, In randomized order, subjects received a single oral dose of 10 mg sinitrodil, 20 mg sin itrodil, 40 mg sinitrodil, isosorbide dinitrate and placebo. Measurements w ere performed before and 45 min after administration of the drugs, Between each drug administration, at least 3 days of wash-out was allowed, Methods The effects of the drugs on large arteries and resistance vessels w ere assessed by their effects on brachial artery compliance and total perip heral resistance, respectively, Results Brachial artery compliance increased gradually with increasing dose s of sinitrodil (by 10, 20 and 27% with 10, 20 and 40 mg sinitrodil, respec tively). Total peripheral resistance index decreased with isosorbide dinitr ate (by 11%)and 40 mg sinitrodil (by 7%), while it remained unchanged with 10 mg and 20 mg sinitrodil. Conclusions The results of this study show that it may be possible to devel op drugs with a higher selectivity for large arteries. Such drugs may be go od candidates to decrease high pulse pressure without substantially decreas ing mean and diastolic blood pressures. J Hypertens 1999, 17:701-705 (C) Li ppincott Williams & Wilkins.