The role of platelet-activating factor (PAF) antagonists and nitric oxide in cardiac actions of PAF. Electrophysiological and morphological study

Electrophysiological and ultrastructural effects of platelet-activating fac tor (PAF) antgonists, WEB 2086 and BN 52021 were compared in isolated guine a-pig hearts preparations. We studied the possible role of nitric oxide (NO ) in electromechanical actions of PAF. Isometric twitches and intracellular action potentials (APs) were recorded from guinea-pig right ventricular pa pillary muscles and left atria. For electron microscopic study the hearts w ere perfused according to Langendorff technique. WEB 2086 (5 x 10(-9)-5 x 1 0(-7) M) significantly shortened the duration of atrial AP without changing the ventricular one, however, BN 52021 decreased both of them. The shorten ing of atrial and ventricular AP duration (APD) by both PAF antagonits were abolished by 4-aminopyridine (10(-3) M), a blocker of one type of K+ chann els (I-Kto). Glibenclamide (10(-6) M) the blocker of ATP-dependent K+ chann els prevented the shortening effect of BN 52021 (10-6 M) on ventricular APD . Electron microscopic study of myocardial samples from hearts subjected to 30 min hypoxia/reoxygenation showed intracellular oedema, intramitochondri al swelling and fragmentation of mitochondrial christae, separation of inte rcalated disc, Pretreatment with WEB 2086 (5 x 10(-7) M) warded off nearly all damage caused by hypoxia/reoxygenation. Both WEB 2086 and NO synthase i nhibitor N-G-nitro-L-arginine methyl esther (L-NAME) (10(-3) M) abolished t he negative inotropic effect of PAF (10(-7), 10(-6) M). L-NAME prevented th e shortening of APD induced by 10(-7) M PAF. These results suggest that PAF may be responsible for myocardial ischemia and the beneficial effects of P AF antagonists in this pathological process could be due to their possible K+ channel stimulator property. data support the possibility that NO contri butes to the cardiac electromechanical alterations induced by PAF.