Vasorelaxant effect of a phosphodiesterase 3 inhibitor, olprinone, on isolated human radial artery.
The radial artery is currently used as a viable arterial conduit for myocardial revascularization. The aims of this study were to identify phosphodiesterase 3 isoenzyme in the human radial artery isolated for coronary artery bypass grafting, and to examine the vasorelaxant effect of a cardiotonic and vasodilating phosphodiesterase 3 inhibitor, 1, 2-dihydro-6-methyl-2-oxo-5-(imidazo[1,2-a]pyridin-6-yl)-3-pyridine carbonitrile hydrochloride monohydrate (olprinone). The phosphodiesterase 3 isoenzyme was separated from the radial artery by DEAE-Sepharose chromatography. Olprinone inhibited the phosphodiesterase 3 activity with an IC(50) value of 1.25 microM. Olprinone relaxed the phenylephrine-induced contractions of endothelium-denuded arterial strips with an EC(50) value of 0. 107+/-0.029 microM (n=5). These findings indicate that the human radial artery possesses phosphodiesterase 3 isoenzyme activity and olprinone causes potent relaxation of the arterial strip in vitro through inhibition of phosphodiesterase 3 isozyme activity.
Adachi
H
H
Cardiovascular Research Unit, Tsukuba Research Laboratories, Eisai Co., Ltd., 1-3, Tokodai 5-Chome, Ibaraki 300-2635, Tsukuba, Japan. h-adachi@hhc.eisai.co.jp
Kamata
S
S
Kodama
K
K
Nagakura
T
T
D004730:Endothelium, Vascular / Q000187:drug effects; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000302:isolation & purification / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D010727:Phosphoric Diester Hydrolases / Q000302:isolation & purification; D011728:Pyridones / Q000494:pharmacology*; D017534:Radial Artery / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
D007093:Imidazoles; D007202:Indicators and Reagents; D007527:Isoenzymes; D010726:Phosphodiesterase Inhibitors; D011728:Pyridones; D014665:Vasodilator Agents; C059498:olprinone; D010727:Phosphoric Diester Hydrolases