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Is it possible to develop drugs that act more selectively on large arteries?
L M Van Bortel1, J J Spek, E J Balkestein
1Department of Pharmacology, Cardiovascular Research Institute Maastricht, Maastricht University, The Netherlands. I.vanbortel@farmaco.unimaas.nl
Journal of Hypertension
|July 14, 1999
Summary
New drug sinitrodil shows promise in selectively targeting large arteries, potentially reducing high pulse pressure without significantly lowering overall blood pressure. This offers a new therapeutic avenue for cardiovascular health.
Area of Science:
- Cardiovascular Pharmacology
- Vascular Physiology
Background:
- High pulse pressure is a significant risk factor for cardiovascular events.
- Selective drugs targeting large arteries may benefit patients with high pulse pressure.
- Current vasodilators often affect both large arteries and resistance vessels.
Purpose of the Study:
- To compare the large artery selectivity of sinitrodil, a novel nitric oxide donor, against isosorbide dinitrate.
- To investigate the potential for developing drugs with enhanced selectivity for large arteries.
Main Methods:
- A double-blind, 5-way crossover study in healthy young men.
- Administration of single oral doses of sinitrodil (10, 20, 40 mg), isosorbide dinitrate, and placebo.
- Assessment of brachial artery compliance (large arteries) and total peripheral resistance (resistance vessels).
Main Results:
- Sinitrodil dose-dependently increased brachial artery compliance (10-27%).
- Isosorbide dinitrate and high-dose sinitrodil (40 mg) reduced total peripheral resistance.
- Lower doses of sinitrodil did not significantly alter total peripheral resistance.
Conclusions:
- Sinitrodil demonstrates greater selectivity for large arteries compared to isosorbide dinitrate.
- Development of drugs with high selectivity for large arteries appears feasible.
- Such selective drugs could effectively lower high pulse pressure while preserving mean and diastolic blood pressures.