[E 4021, a cGMP phosphodiesterase inhibitor, is a selective pulmonary vasodilator in chronically hypoxic pulmonary hypertensive rats].

Abstract

To test whether a potent cGMP-specific phosphodiesterase inhibitor, E 4021, is a selective pulmonary vasodilator in pulmonary hypertension, we studied its acute hemodynamic effects in conscious, chronically hypoxic pulmonary hypertensive rats. Chronically hypoxic pulmonary hypertension was induced by keeping adult Sprague-Dawley rats in a hypobaric chamber for 3 weeks. Two days after catheterization. E 4021 was injected intravenously at doses of 3, 10, 30, 100, 300, and 1,000 micrograms/kg at 10-min intervals. E 4021 caused significant decreases in mean pulmonary arterial pressure of 11 +/- 5, 12 +/- 6, and 18 +/- 5% at doses of 100, 300, and 1,000 micrograms/kg, respectively. In contrast to its depressor effect on mean pulmonary arterial pressure, E 4021 decreased mean systemic arterial pressure significantly (by 9 +/- 2%) at a dose of 1,000 micrograms/kg only. Heart rate and cardiac output were unchanged after the administration of E 4021. Tissue cGMP-specific phosphodiesterase activity was markedly higher in lung than in aorta. These results indicate that E 4021 is a relatively selective pulmonary vasodilator in chronically hypoxic pulmonary hypertensive rats. We conclude E 4021 may be useful for the treatment of pulmonary hypertension.

• Authors: K Yamaguchi, M Oka, M Nishino, N Hanasato, S Kira, Y Fukuchi
• Journal: Nihon Kokyuki Gakkai zasshi = the journal of the Japanese Respiratory Society (Nihon Kokyuki Gakkai Zasshi) Vol. 36 Issue 1 Pg. 23-8 (Jan 1998) ISSN: 1343-3490 [Print] Japan
• PMID: 9611972 (Publication Type: Journal Article)

Chemical References

• E 4021
• Phosphodiesterase Inhibitors
• Piperidines
• Quinazolines
• Vasodilator Agents
• 3',5'-Cyclic-GMP Phosphodiesterases

Topics

• 3',5'-Cyclic-GMP Phosphodiesterases (metabolism)
• Animals
• Blood Pressure (drug effects)
• Chronic Disease
• Hypertension, Pulmonary (drug therapy)
• Hypoxia (drug therapy)
• Lung (enzymology)
• Male
• Phosphodiesterase Inhibitors (pharmacology, therapeutic use)
• Piperidines (pharmacology, therapeutic use)
• Pulmonary Artery (physiopathology)
• Quinazolines (pharmacology, therapeutic use)
• Rats
• Rats, Sprague-Dawley
• Vasodilator Agents (therapeutic use)