Effects of a phosphodiesterase 3 inhibitor, olprinone, on rhythmical change in tension of human gastroepiploic artery.
The gastroepiploic artery, used widely as a conduit in coronary artery bypass grafting, has high vasospasticity. The aims of this study were to examine the vasorelaxant effects of three phosphodiesterase 3 (PDE3) inhibitors, olprinone, milrinone and amrinone, on isolated gastroepiploic arterial preparations in comparison with a calcium channel blocker diltiazem, and to confirm the mRNA expression of PDE3A isoenzyme using reverse transcription-polymerase chain reaction (RT-PCR) in the human gastroepiploic artery isolated from stomach removed in cancer surgery. In endothelium-denuded gastroepiploic arterial preparations, phenylephrine (100 microM) produced spontaneous, rhythmical changes in tension consisting of repeated contraction and relaxation. Olprinone at a concentration of 10 microM (n=6) significantly inhibited the frequency (2.7+/-1.1 times/30 min vs. 6.2+/-0.7 times/30 min in the vehicle group), maximum tension (1.7+/-0.6 g vs. 3.6+/-0.6 g in the vehicle group) and minimum tension (0.6+/-0.2 g vs. 1.7+/-0.3 g in the vehicle group) of rhythmical changes. Such potency is comparable to that of diltiazem, but is stronger than milrinone and amrinone. RT-PCR using PDE3A- or PDE3B-specific oligonucleotide primer demonstrated the existence of PDE3A sequence in the gastroepiploic artery. These results suggest that olprinone, a potent PDE3A inhibitor, would be suitable for protecting against perioperative spasm during coronary artery bypass graft surgery.
Adachi
Hideyuki
H
Regulatory Science Operations Department, Eisai Co., Ltd., Koishikawa 4-6-10, Bunkyo-ku, Tokyo 112-8088, Japan. h-adachi@hhc.eisai.co.jp
Kakiki
Motoharu
M
Kishi
Yoshihiko
Y
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D000676:Amrinone / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D004110:Diltiazem / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D024405:Gastroepiploic Artery / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D066298:In Vitro Techniques; D020105:Milrinone / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000201:enzymology; D011728:Pyridones / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism*; D013997:Time Factors; D014664:Vasodilation / Q000187:drug effects
D002121:Calcium Channel Blockers; D004791:Enzyme Inhibitors; D007093:Imidazoles; D011728:Pyridones; D012333:RNA, Messenger; C059498:olprinone; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; C517287:PDE3A protein, human; C517291:PDE3B protein, human; D004110:Diltiazem; D020105:Milrinone; D000676:Amrinone