[Effects of bufadienolides and some kinds of cardiotonics on guinea pig hearts].
Effects of bufadienolides such as bufalin (BF) and cinobufagin (CB), the main components of Senso (Ch'an Su), on myocardial Na+,K(+)-ATPase activity, the cardiotonic activity in vivo and the action potential of isolated guinea pig papillary muscle cells were compared with those of other cardiotonic drugs. 1) The rank order of potency for inhibition of myocardial Na+,K(+)-ATPase activity was BF greater than digoxin (DG) greater than digitoxin (DT) greater than telocinobufagin greater than gamabufotalin greater than cinobufotalin greater than CB greater than g-strophanthin (GS) greater than digitoxigenin (DTG) greater than resibufogenin (RB) when compared at the 50% inhibitory concentration. 2) In isolated papillary muscle cells, CB shortened the action potential duration (APD) dose-dependently. The order of potency for shortening of APD was GS greater than CB greater than DTG much greater than DT. 3) In open-chest guinea pigs, intraduodenal administration of BF or CB increased the myocardial contractile force (MCF), but did not affect the heart rate. The order of potency for increase in MCF was as follows: methyldigoxin, proscillaridin greater than BF greater than CB greater than DG greater than Senso much greater than DT, DTG, RB. These results indicate that CB has a shortening effect on APD and an inhibitory effect on Na+,K(+)-ATPase activity along with its cardiotonic effect, like GS.
Hirai
Y
Y
Research Laboratories, Kyushin Pharmaceutical Co., Ltd., Tokyo, Japan.
Morishita
S
S
Ito
C
C
Sakanashi
M
M
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002018:Bufanolides / Q000008:administration & dosage / Q000494:pharmacology*; D002316:Cardiotonic Agents / Q000494:pharmacology*; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000201:enzymology; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors
D002018:Bufanolides; D002316:Cardiotonic Agents; D000254:Sodium-Potassium-Exchanging ATPase; C002471:cinobufagin; C022777:bufalin