Platelet-activating factor and the release of a platelet-derived coronary artery vasodilator substance in the canine.

Abstract

which is released by stimulated neutrophils and platelets, possesses the ability to alter vascular tone and permeability and to activate various formed blood elements. We have characterized the hemodynamic effects of intracoronary injections of plateletactivating factor and the influences of pharmacological blockade and platelet depletion on its activity. Intracoronary injections of platelet-activating factor produced maximum increases in left circumflex coronary artery blood flow of 55 ± 8, 52 ± 8, and 52 ± 7 ml/min at 0.5, 1.0, and 2.0 nM, respectively. Only modest changes in systemic arterial blood pressure and regional developed isometric contractile force were associated with the intracoronary artery administration of platelet-activating factor over the range of doses studied. The increase in left circumflex coronary artery blood flow in response to platelet-activating factor was attenuated (44%), but not prevented, by pretreatment with diphenhydramine, (4 mg/kg, iv), and was not affected by pretreatment with aspirin (20 mg/kg, iv) or the systemic administration of the serotonin receptor antagonist, methysergide. The coronary vasodilator response to platelet-activating factor was reduced significantly by the induction of thrombocytopenia (95 ± 3% platelet depletion) through the administration of sheep-derived canine platelet antiserum. The intracoronary artery injection of platelet-rich plasma activated with platelet-activating factor into thrombocytopenic dogs produced a significantly greater increase in coronary artery blood flow than the injection of either non-activated platelet-rich plasma or platelet-depleted plasma to which platelet-activating factor was added. Similar changes in coronary artery blood flow could be obtained with the intracoronary artery injection of cell-free supernates from washed platelets activated with platelet-activating factor. The observed results suggest that circulating platelets, when exposed to platelet-activating factor, can release a coronary dilator substance, and that the coronary artery dilation is not prevented by pharmacological receptor antagonists for histamine, serotonin, or inhibitors of cyclooxygenase. (CircRes 58: 218-229, 1986)

Occupancy of platelet receptors for platelet-activating factor in patients with septicemia.

“…In contrast, PAF-activated polymorphonuclear leukocytes were unable to cause lung damage in the same experimental model. Similar platelet-dependent pathways have been reported for the role of PAF on bronchoconstriction in the guinea pig (16), and in coronary artery vasodilatation in the canine (17).…”

PAF Antagonists as Potential Therapeutic Agents in Cardiac Anaphylaxis and Myocardial Ischemia

“…In contrast to these results, intracoronary injection of PAF into anesthetized dogs has been shown to increase coronary artery blood flow without affecting contractility and systemic blood pressure (41). The PAF response was markedly suppressed in animals depleted in their platelets by administration of sheep-derived canine platelet antiserum.…”

Antagonism of vasoconstriction induced by platelet‐activating factor in guinea‐pig perfused hearts by selective platelet‐activating factor receptor antagonists

“…Thus, the relatively unopposed nature of Paf-induced vasoconstriction may contribute to its duration of action. Interestingly, intracoronary administration of Paf in anaesthetized dogs releases a platelet-derived coronary artery vasodilator substance (Jackson et al, 1986).…”