ABSTRACT
The effects of platelet activating factor (PAF) and three its antagonists on the transmembrane intracellular potentials and stimulated (0.5 Hz) contraction amplitude (CA) of the left auricle has been studied. PAF (1-5 X 10(-7) M) was added to the standard Tyrode solution or the same perfusing solution with 15 mM K+, and 6 mM Ca++ (t = 30 degrees C, pH = 7,2). PAF induced the straight cardio-depressing action: the CA always was suppressed during 20 min. The electrical activity was depressed in parallel; in the Tyrode the action potential (AP) duration was lowered, but in the atrial depolarized preparations PAF resulted in a decrease of the slow calcium potential (Ca-AP) amplitude from 100% to 20.2 +/- 2.0%. After 20 min PAF-acting the perfusing solutions contained also one of PAF-antagonists. Antagonist U-66985 led to the weakening of the PAF-depressing effects in the myocardium U-66985 is also able to increase electrical and mechanical activity in myocardium depressed by the blood serum from patients with virulent infections.
Subject(s)
Heart/drug effects , Myocardial Contraction/drug effects , Platelet Activating Factor/pharmacology , Action Potentials/drug effects , Animals , Azepines/pharmacology , Heart/physiology , Heart Atria/drug effects , Humans , Hypnotics and Sedatives/pharmacology , In Vitro Techniques , Infections/blood , Perfusion , Platelet Activating Factor/antagonists & inhibitors , RabbitsABSTRACT
The cardiodepressive effect of PAF has been studied on the electrical and mechanical activities of isolated auricles of guinea pig. Intracellular resting potential, action potential (AP) and isometric contractions elicited by electrical stimulation (0.5 Hz) were measured. PAF (10(-7) M) induced negative inotropic effect, which reached its peak after 5 min with 23.5 +/- 6.6% in respect to prechallenge values (n = 8). After 20 min negative inotropic effect relaxed to 39.6 +/- 8.8%. 1 min after the beginning of washing in Tyrode solution, positive inotropic effect of PAF was evident, that reached its peak (217 +/- 49.5%) after 2 min, decayed after 5-10 min to normal values. PAF did not modify the resting membrane potential, produced a decrease in the amplitude and Vmax of the upstroke AP, shortened the AP duration. Ca-AP and contractions, elicited in partially depolarized myocardium were decreased by PAF (10(-7) M). PAF-produce the change of the AP and the negative effect on auricle contractile force was inhibited in muscles pretreated with 3mM 4 aminopyridine. Histamine (10(-4) M) was also capable of neutralizing the depressant effect of PAF. The obtained results suggested that PAF effects on the membrane of cardiac cells could be related to a change in Ca and K conductance.
