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Selective pulmonary vasodilation induced by aerosolized zaprinast
F Ichinose1, C Adrie, W E Hurford
1Department of Anaesthesia and Critical Care, Massachusetts General Hospital, Boston 02114, USA.
Anesthesiology
|February 26, 1998
Summary
Inhaled zaprinast, a phosphodiesterase inhibitor, dilates pulmonary circulation and enhances nitric oxide (NO) effects. This combination may treat pulmonary hypertension.
Area of Science:
- Pharmacology
- Cardiovascular Physiology
Background:
- Zaprinast inhibits cyclic guanosine monophosphate (cGMP)-selective phosphodiesterase.
- It augments smooth muscle relaxation induced by endothelium-dependent vasodilators like nitric oxide (NO).
Purpose of the Study:
- To investigate the effects of inhaled nebulized zaprinast, alone and with inhaled NO.
- To assess potential therapeutic applications in pulmonary hypertension.
Main Methods:
- Eight lambs with induced pulmonary hypertension inhaled NO (5 and 20 ppm).
- They subsequently inhaled zaprinast aerosols at various concentrations (10-50 mg/ml).
- Combined NO and zaprinast inhalation was also studied.
Main Results:
- Inhaled NO and zaprinast selectively dilated the pulmonary vasculature.
- Zaprinast potentiated and prolonged NO-induced pulmonary vasodilation.
- Both agents increased transpulmonary cGMP release; zaprinast's vasodilation lasted longer than NO's.
Conclusions:
- Aerosolized cGMP-selective phosphodiesterase inhibitors, alone or with NO, show promise.
- This noninvasive method may be beneficial for treating acute or chronic pulmonary hypertension.