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Effects of platelet activating factor on contractile force and 45 Ca fluxes in guinea‐pig isolated atria
Author(s) -
Diez J.,
Delpón E.,
Tamargo J.
Publication year - 1990
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1990.tb15800.x
Subject(s) - verapamil , inotrope , platelet activating factor , phentolamine , medicine , chemistry , endocrinology , propranolol , isoprenaline , antagonist , chronotropic , atrium (architecture) , atropine , guinea pig , calcium , biology , heart rate , receptor , stimulation , blood pressure , atrial fibrillation
1 The effects of platelet activating factor (PAF) were studied on the electromechanical properties and 45 Ca 2+ fluxes of guinea‐pig isolated atria. 2 Both in spontaneously beating and electrically driven atria, PAF (10 −12 ‐10 −7 m ) increased atrial rate but produced a biphasic effect on contractile force. At low concentrations (up to 10 −10 m ) it produced a positive inotropic effect, while at higher concentrations PAF exerted a negative inotropic effect. A similar biphasic effect was observed in the slow contractions elicited by isoprenaline in K + ‐depolarized atrial fibres. 3 The positive inotropic effect of PAF was prevented by verapamil, whereas pretreatment of atria with propranolol, phentolamine, indomethacin or atropine did not modify its positive and negative inotropic actions. BN 52021, a specific PAF antagonist, abolished both the positive and negative inotropic effects. 4 PAF had no effect on the characteristics of the action potentials recorded in either normally polarized or K + ‐depolarized (slow action potential) atrial fibres. 5 At concentrations at which it increased contractile force, PAF potentiated the contractile responses to Ca 2+ (0.9‐9 m m ), whereas at negative inotropic concentrations it inhibited them. The negative inotropic effect of PAF was partially reversed in 70% Na + medium. 6 At 10 −11 m , PAF increased 45 Ca 2+ uptake and reduced the rate coefficient ( k cm for the 45 Ca 2+ efflux. This increase in 45 Ca 2+ uptake was abolished in atria pretreated with verapamil or BN 52021. However, 10 −7 μ PAF modified neither 45 Ca 2+ uptake nor efflux in atrial muscle. 7 These results suggest that in guinea‐pig atria the biphasic inotropic effects of PAF cannot be explained through modifications in the slow inward Ca 2+ current or in Na + ‐Ca 2+ exchange, but may be related to changes in trans‐sarcolemmal Ca 2+ entry mediated by specific PAF receptors.