Cyclic blood flow variations induced by platelet-activating factor in stenosed canine coronary arteries despite inhibition of thromboxane synthetase, serotonin receptors, and alpha-adrenergic receptors. Circulation 1985 Aug;72(2):397-405
Date
08/01/1985Pubmed ID
2988822DOI
10.1161/01.cir.72.2.397Abstract
The phospholipid platelet-activating factor (PAF) stimulates platelet aggregation and coronary vasoconstriction. In this study we determined whether PAF alters coronary flow patterns in vivo in a canine preparation with concentric coronary artery stenosis. This preparation is characterized by cyclic flow variations in coronary blood flow associated with transient platelet aggregation at the site of the coronary constriction. Thirty-nine male mongrel dogs were used in three protocols. In protocol 1, PAF (10(-9) or 10(-8) mol/min) was infused into the coronary artery proximal to the stenosis to determine (1) whether PAF induces cyclic flow variations and (2) whether PAF has an effect on systemic hemodynamics. Cyclic flow variations were induced in three of six dogs; in these animals, mean arterial pressure decreased by 5.5% and 42.1% 10 min after infusion of the lower and higher dose of PAF. In protocol 2, cyclic flow variations were abolished with either the thromboxane synthetase inhibitor UK38485 (mean dose 2.2 mg/kg iv), the serotonin antagonist ketanserin (0.5 mg/kg iv), or the alpha 2-adrenergic antagonist yohimbine (2 mg/kg iv). Subsequent administration of PAF restored the frequency of cyclic flow variations to the preantagonist levels. Thromboxane (Tx) B2 and 6-keto-PGF1 alpha, the stable metabolites of TxA2 and prostacyclin, respectively, were measured in blood obtained distal to the coronary stenosis. TxB2 levels increased substantially during cyclic flow variations and were returned to control values with the thromboxane synthetase inhibitor UK38485. Infusion of PAF subsequently restored cyclic flow variations without altering coronary arterial coronary arterial TxB2 levels.(ABSTRACT TRUNCATED AT 250 WORDS)
Author List
Apprill P, Schmitz JM, Campbell WB, Tilton G, Ashton J, Raheja S, Buja LM, Willerson JTAuthor
William B. Campbell PhD Professor in the Pharmacology and Toxicology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
6-Ketoprostaglandin F1 alphaAdrenergic alpha-Antagonists
Animals
Arteriosclerosis
Coronary Circulation
Coronary Disease
Dogs
Hemodynamics
Imidazoles
Male
Platelet Activating Factor
Platelet Aggregation
Serotonin Antagonists
Thromboxane B2
