Actions of platelet-activating factor on isolated rat hearts.
The actions of Platelet-Activating Factor (PAF) on isolated rat hearts were investigated. In a dose-dependent manner PAF decreased peak systolic pressure and maximum rate of rise of intraventricular pressure (+dP/dt(max]. PAF dose-dependently decreased coronary flow, prolonged the P-R interval of the EKG, and decreased heart rate. These actions of PAF were only partially blocked by drugs blocking receptors for PAF (CV 3988, WEB 2086), thromboxanes (ONO 3708), or leukotrienes (FPL 55712, L-655,240) or by a blocker of eicosanoid production (ibuprofen). Since depressed contractions will of themselves reduce coronary flow, PAF's action on flow was also investigated in hearts whose contractions were blocked by elevated potassium concentrations plus tetrodotoxin. Such treatment did not prevent PAF reducing coronary flow, indicating that a direct vasoconstriction occurred. The reductions in coronary flow in non-contracting hearts induced by PAF were equal to those induced by the coronary vasoconstrictors vasopressin and ergonovine under the same conditions. In order to isolate direct effects of PAF on myocardial contractile cells from effects mediated via changes in coronary flow, PAF was given to hearts maximally dilated by a concentration of nifedipine (0.03 microM) which had no effect on contractility. This concentration of nifedipine increased flow from 15.5 +/- 1.4 mL/min to 18.1 +/- 2.4 mL/min. In the presence of this nifedipine-induced vasodilation, PAF still exhibited negative inotropic actions, but without reducing coronary flow. Thus the effects of PAF on isolated rat hearts involve direct actions on both myocardial contracting cells and on coronary vessels.(ABSTRACT TRUNCATED AT 250 WORDS)
Pugsley
M K
MK
Department of Pharmacology and Therapeutics, University of British Columbia, Vancouver, Canada.
Salari
H
H
Walker
M J
MJ
D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography / Q000187:drug effects; D006321:Heart / Q000187:drug effects*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009543:Nifedipine / Q000494:pharmacology; D010477:Perfusion; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D010980:Platelet Membrane Glycoproteins; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000187:drug effects; D043562:Receptors, G-Protein-Coupled; D013779:Tetrodotoxin / Q000494:pharmacology
D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; C039351:platelet activating factor receptor; D013779:Tetrodotoxin; D009543:Nifedipine