Effects of beraprost on the transmembrane potentials of guinea-pig ventricular muscles during normoxia and hypoxia-reoxygenation.
1. The present study was performed to determine whether beraprost, a new stable analogue of prostacyclin, may exert beneficial effects on the transmembrane action potentials during normoxia and hypoxia-reoxygenation in isolated right ventricular muscles of the guinea-pig. 2. Under normal oxygenation, beraprost (0.01-100 mumol-1) had no effects on the electrophysiological parameters. 3. Hypoxic conditions induced a decrease in action potential duration (APD) without affecting other action potential parameters. Beraprost inhibited this hypoxia-induced decrease in APD. However, beraprost had no effect on the decrease in contractile force induced by hypoxia, whereas it significantly improved the recovery of contractile force after reoxygenation. 4. Pinacidil-induced shortening of APD was not antagonized by beraprost. 5. Hypoxia significantly decreased the myocardial adenosine triphosphate (ATP) level, which was also prevented by beraprost. 6. These results suggested that beraprost may inhibit the hypoxia-induced shortening of APD by some mechanisms which contribute to the maintenance of muscle ATP level.
Ueno
Y
Y
Toray Industries, Inc., Basic Research Laboratories, Kamakura, Japan.
Shigenobu
K
K
Nishio
S
S
D000200:Action Potentials / Q000187:drug effects; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D011464:Epoprostenol / Q000031:analogs & derivatives* / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D006352:Heart Ventricles / Q000187:drug effects; D000860:Hypoxia / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism; D010100:Oxygen / Q000494:pharmacology; D010210:Papillary Muscles / Q000187:drug effects; D020110:Pinacidil; D014665:Vasodilator Agents / Q000494:pharmacology
D006146:Guanidines; D014665:Vasodilator Agents; C048081:beraprost; D020110:Pinacidil; D000255:Adenosine Triphosphate; D011464:Epoprostenol; D010100:Oxygen