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

V. Kecskeméti, I. Balogh

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Abstract

Electrophysiological and ultrastructural effects of platelet-activating factor (PAF) antgonists, WEB 2086 and BN 52021 were compared in isolated guinea-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 papillary muscles and left atria. For electron microscopic study the hearts were perfused according to Langendorff technique. WEB 2086 (5 × 10-9 - 5 × 10-7 M) significantly shortened the duration of atrial AP without changing the ventricular one, however, BN 52021 decreased both of them. The shortening 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+ channels (IKto). Glibenclamide (10-6 M) the blocker of ATP-dependent K+ channels 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, intramitochondrial swelling and fragmentation of mitochondrial christae, separation of intercalated disc. Pretreatment with WEB 2086 (5 × 10-7 M) warded off nearly all damage caused by hypoxia/reoxygenation. Both WEB 2086 and NO synthase inhibitor NG-nitro-L-arginine methyl esther (L-NAME) (10-3 M) abolished the negative inotropic effect of PAF (10-7, 10-6 M). L-NAME prevented the 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 PAF antagonists in this pathological process could be due to their possible K+ channel stimulator property. These data support the possibility that NO contributes to the cardiac electromechanical alterations induced by PAF.

Original languageEnglish
Pages (from-to)723-735
Number of pages13
JournalJournal of Physiology and Pharmacology
Volume51
Issue number4
Publication statusPublished - Dec 1 2000

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Keywords

  • Cardiac action potential
  • Cardiac ultrastructure
  • Glibenclamide
  • Nitric oxide
  • Platelet activating factor
  • Platelet activating factor antagonists

ASJC Scopus subject areas

  • Physiology
  • Pharmacology

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