Synergistic interaction of endogenous platelet-activating factor and vasopressin in generating angina in rats

János Nemcsik, Krisztina Kordás, József Egresits, Ferenc László, Ferenc A. László, Imre Pávó, Éva Morschl

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Abstract

We examined the involvement of endogenous vasopressin and platelet-activating factor (PAF) in the pathogenesis of two types of experimental angina in urethane-anaesthetised male Wistar rats. In the first model, epinephrine (10 μg kg -1) was injected into the tail vein, followed at the development of the maximum blood pressure response, i.e., 30 s later, by phentolamine (15 mg kg -1). In the second model, the vasopressin V 1 receptor agonist ornithine-vasopressin (ornipressin; 0.5 IU kg -1, i.v.) was administered. The heart rate, mean arterial blood pressure and surface electrocardiogram (ECG, standard lead II) were registered simultaneously. As a measure of myocardial ischaemia, at 1 min after phentolamine or ornipressin administration, we found significant ST-segment depression, lasting for more than 10 or 5 min, respectively. Pretreatment (15 min, s.c.) with the vasopressin V 1 receptor antagonist Mca 1,Tyr(Me) 2AVP (the Manning peptide; 0.02-0.2 μg kg -1) or the platelet-activating factor receptor antagonist ginkgolide B (BN 52021; 0.25-2.5 mg kg -1) alone caused a dose-dependent reduction of the ST-segment depression. Concurrent administration of the two antagonists in their threshold doses (0.02 μg kg -1 and 0.25 mg kg -1) also attenuated the ST-segment depression in both models. Neither antagonist affected the blood pressure or heart rate changes throughout the studies. Our results suggest that endogenous vasopressin and platelet-activating factor interact synergistically in provoking myocardial ischaemia in vivo in experimental angina in the rat.

Original languageEnglish
Pages (from-to)195-202
Number of pages8
JournalEuropean Journal of Pharmacology
Volume498
Issue number1-3
DOIs
Publication statusPublished - Sep 13 2004

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Keywords

  • Experimental angina
  • Pathogenesis of myocardial ischaemia
  • Platelet-activating factor
  • Synergistic interaction
  • Vasopressin

ASJC Scopus subject areas

  • Pharmacology

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