PT  - JOURNAL ARTICLE
AU  - D A Robertson
AU  - D Y Wang
AU  - C O Lee
AU  - R Levi
TI  - Negative inotropic effect of platelet-activating factor: association with a decrease in intracellular sodium activity.
DP  - 1988 Apr 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 124--128
VI  - 245
IP  - 1
4099  - http://jpet.aspetjournals.org/content/245/1/124.short
4100  - http://jpet.aspetjournals.org/content/245/1/124.full
SO  - J Pharmacol Exp Ther1988 Apr 01; 245
AB  - Platelet-activating factor (PAF) is an autacoid whose cardiovascular actions include a potent negative inotropic effect. The mechanism of this decrease in myocardial contractility is still at issue, as both a decrease and an increase in trans-sarcolemmal Ca++ influx have been reported. Because changes in intracellular sodium activity (aiNa) are known to influence myocardial contractility, we investigated whether PAF affects aiNa. Thus, we have measured contractile responses to PAF (1 nM-1 microM) in isolated guinea pig right ventricular papillary muscles paced at constant rate, and recorded transmembrane action potential and aiNa with conventional and sodium-selective microelectrodes, respectively. Our findings suggest that PAF does not affect slow inward Ca++ current, because PAF neither affected nor prevented histamine-induced restoration of contractile responses in K+-depolarized papillary muscles. On the other hand, we found the negative inotropic effect of PAF to be associated with a shortening of the action potential duration and with a decrease in aiNa. The specific PAF antagonist compound CV-3988 inhibited all three electro-mechanical responses. Our findings imply that the decrease in contractile force caused by PAF may depend on the reduction in aiNa; as aiNa falls, intracellular Ca++ may be lost via the Na+/Ca++ exchange and contractility decreases. The shortening of the action potential duration by PAF may reflect a decrease in Na+ influx and the consequent reduction in aiNa.