In vivo and in vitro assessment of the cardiovascular effects of 8-(benzylthio)-N6-n-butyl-cyclic AMP.
In the canine heart-lung preparation (HLP) and the anesthetized open-chest dog, both 8-(Benzylthio)-N6-n-butyl-cyclic AMP (BTB-cyclic AMP) (10 times more potent) and dibutyryl-cyclic AMP (DB-cyclic AMP) produced a definite positive inotropic effect (PIE) and an increase in the coronary blood flow with either no change (HLP) or a slight increase (anesthetized animal) (BTB-cyclic AMP) and a definite increase in the heart rate (DB-cyclic AMP). In the isolated atrial preparations of the guinea pig (AG), BTB-cyclic AMP produced a slight PIE at 3 X 10(-5) M and a negative chronotropic effect at 3 X 10(-4) M. Aminophylline reversed the latter to the positive one, while potentiating the former. At 10(-3) M marked positive inotropic and chronotropic effects were observed. DB-cyclic AMP was without effects. In the right ventricular papillary muscle preparations of the guinea pig (PMG), both compounds produced PIE. BTB-cyclic AMP initiated a contraction (AG) and a "slow" action potential (PMG) in partially depolarized preparations. Both of these effects were abolished by diltiazem. BTB-cyclic AMP (10(-3) M) suppressed the heart rate increase induced by isoproterenol in right AG. It was concluded that BTB-cyclic AMP was a cardiotonic agent with a relatively weak positive chronotropic effect and that the cardiotonic effect was ascribable to the initiation of slow action potentials and related contractions.
M
M
Nakazawa
K
K
Takeda
Y
Y
Nakagawa
H
H
Tamatsu
K
K
Matsui
H
H
Nakahara
T
T
Kimura
T
T
Kawada
S
S
Imai
D000758:Anesthesia; D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects; D000242:Cyclic AMP / Q000031:analogs & derivatives* / Q000494:pharmacology; D004285:Dogs; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D010210:Papillary Muscles / Q000187:drug effects; D013997:Time Factors
C040965:8-benzylthio-N(6)-n-butyladenosine cyclic-3,5'-monophosphate; D000242:Cyclic AMP; D007545:Isoproterenol