Positive inotropic and chronotropic effects of beraprost sodium, a stable analogue of prostacyclin, in isolated guinea pig myocardium.
1. Inotropic and chronotropic effects of beraprost sodium (beraprost), a chemically stable prostacyclin analogue, were examined in isolated myocardial preparations of guinea pigs. 2. In the left atria, 10(-9) - 10(-7) M beraprost had no significant effect on the contractile force, but 10(-6) and 10(-5) M produced a concentration-dependent positive inotropic response. This effect was antagonized by S-145, a potent and selective thromboxane A2 (TXA2) receptor antagonist, but not by propranolol. 3. Beraprost, from 10(-9) to 10(-5) M, had no significant inotropic effect in the right ventricular papillary muscles. 4. In the right atria, 10(-9) and 10(-8) M beraprost had no significant effect, but 10(-7) - 10(-5) M caused an increase in beating rate; this effect was not affected by S-145. 5. The present study demonstrates that beraprost has positive inotropic and chronotropic effects at high doses on isolated guinea pig atria. The inotropic effect may be mediated by the TXA2 receptor, but some mechanism other than the TXA2 receptor is responsible for the chronotropic effect.
Ueno
Y
Y
Toray Industries, Inc., Basic Research Laboratories, Kanagawa, Japan.
Okazaki
S
S
Isogaya
M
M
Nishio
S
S
Tanaka
H
H
Kato
Y
Y
Shigenobu
K
K
D000319:Adrenergic beta-Antagonists; D000818:Animals; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology; D011464:Epoprostenol / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology; D006168:Guinea Pigs; D006325:Heart Atria / Q000187:drug effects; D006352:Heart Ventricles / Q000187:drug effects; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D010210:Papillary Muscles / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011433:Propranolol / Q000494:pharmacology; D011982:Receptors, Prostaglandin
D000319:Adrenergic beta-Antagonists; D001643:Bridged Bicyclo Compounds; D005229:Fatty Acids, Monounsaturated; D010975:Platelet Aggregation Inhibitors; D011982:Receptors, Prostaglandin; C056566:S 145; C048081:beraprost; D011433:Propranolol; D011464:Epoprostenol