Synergistic interaction of endogenous platelet-activating factor and vasopressin in generating angina in rats.
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 microg 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 V1 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 V1 receptor antagonist Mca1,Tyr(Me)2AVP (the Manning peptide; 0.02-0.2 microg 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 microg 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.
Nemcsik
János
J
Institute of Experimental Medicine, Hungarian Academy of Sciences, Szigony u. 43, H-1083 Budapest, Hungary.
Kordás
Krisztina
K
Egresits
József
J
László
Ferenc
F
László
Ferenc A
FA
Pávó
Imre
I
Morschl
Eva
E
D000787:Angina Pectoris / Q000209:etiology / Q000378:metabolism*; D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists; D001127:Arginine Vasopressin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D004224:Diterpenes / Q000008:administration & dosage / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004562:Electrocardiography; D004837:Epinephrine / Q000008:administration & dosage / Q000494:pharmacology; D046934:Ginkgolides; D006339:Heart Rate / Q000187:drug effects; D006727:Hormone Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D007275:Injections, Intravenous; D007783:Lactones / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D017202:Myocardial Ischemia / Q000139:chemically induced / Q000150:complications / Q000503:physiopathology; D009951:Ornipressin / Q000008:administration & dosage / Q000494:pharmacology; D010646:Phentolamine / Q000008:administration & dosage / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D017483:Receptors, Vasopressin / Q000819:agonists; D013997:Time Factors; D014662:Vasoconstrictor Agents / Q000008:administration & dosage / Q000494:pharmacology; D014667:Vasopressins / Q000378:metabolism*
D065092:Antidiuretic Hormone Receptor Antagonists; D004224:Diterpenes; D046934:Ginkgolides; D006727:Hormone Antagonists; D007783:Lactones; D010972:Platelet Activating Factor; D017483:Receptors, Vasopressin; D014662:Vasoconstrictor Agents; D014667:Vasopressins; D001127:Arginine Vasopressin; D009951:Ornipressin; C025043:vasopressin, 1-(1-mercaptocyclohexaneacetic acid)-2-(O- methyl-L-tyrosine)-8-L-arginine-; C045856:ginkgolide B; D004837:Epinephrine; D010646:Phentolamine