Cardiovascular effects of platelet‐activating factor

Abstract

Sudden release of platelet-activating factor (PAF) into the circulation can cause hypotension, tachycardia, and circulatory collapse. To further examine this response, we performed detailed studies of cardiovascular function after PAF administration to young domestic pigs and newborn piglets. Our results indicate that circulatory dysfunction after PAF reflects severe constriction of pulmonary resistance vessels and consequent acute right ventricular failure. Although PAF-induced coronary artery constriction and contractile depression may be complicating problems, left ventricular underperfusion and dysfunction after PAF are mainly the result of systemic arterial hypotension and diminished left ventricular filling. The adverse hemodynamic effects of PAF are accompanied by substantial release of thromboxane A2 (TxA2). These effects are mimicked by the TxA2 agonist U-46619 and partially blocked by specific and nonspecific inhibitors of TxA2 synthesis (OKY-046 and indomethacin). Even more potent blockade of PAF action is exerted by the TxA2 receptor blocker, SQ 29,548. Taken together, these findings indicate that severe pulmonary vascular constriction and hemodynamic collapse soon after intravenous PAF are at least partially mediated by PAF-induced TxA2 release. Tachyphylaxis to PAF influence has been observed in studies of leukocyte and platelet function. We hypothesized that tachyphylaxis to PAF might also occur in our studies of constrictor responses in pulmonary vessels. Recently, we have examined the capacity of PAF to produce sustained pulmonary vasoconstriction in open-chested, anesthetized newborn piglets. Infusions sufficient to produce 100% increase in mean pulmonary artery pressure after 3 min showed no loss of efficacy when sustained for 30 min.(ABSTRACT TRUNCATED AT 250 WORDS)

Mechanisms of pulmonary vasoconstriction and bronchoconstriction produced by PAF in the guinea‐pig: role of platelets and cyclo‐oxygenase metabolites

“…(Laurindo et al, 1989). In pigs, a severe increase of pulmonary vascular resistance, depending only partially on thromboxane A2 (TXA2) synthesis, was indicated as the primary mechanism early in the course of PAF-induced shock (Goldstein et al, 1991). Pulmonary vasoconstriction almost completely due to TXA2 synthesis was recently also observed in dogs (Yamanaka et al, 1992), even though it was considered to be of minor importance in the hypotension caused by PAF.…”

Nitric oxide (NO) modulation of PAF‐induced cardiopulmonary action: interaction between NO synthase and cyclo‐oxygenase‐2 pathways

“…Intravenous administration of PAF has been shown to induce systemic hypotension, pulmonary vascular hypertension and bronchoconstriction (Braquet et al, 1987;Goldstein et al, 1991). It is also well established that pulmonary functions are modulated by nitric oxide (NO) ± the endogenous gas released from both vascular endothelium (Ignarro et al, 1987;Palmer et al, 1987) and airway epithelium (Folkerts & Nijkamp, 1998) ± which contributes to the maintenance of vascular and bronchial tone.…”

Differential Effects of Tumor Necrosis Factor-α and Platelet-Activating Factor on Bovine Pulmonary Artery Endothelial Cells in Vitro

“…The blood concentration of PAF, like TNFa, is also increased during endotoxemia [6]. The lipid mediator also evokes many of the cardiopulmonary effects seen during endotoxemia [7], and a PAF receptor antagonist has been shown to improve survival when given before the onset of endotoxemia [8]. Because these two mediators (TNFa and PAF) appear to play important roles in the pathophysiology of endotoxemia, and because a major sequela of endotoxemia is increased macromolecular permeability across pulmonary vascular endothelium, we directly compared the effects of TNFa and PAF on cultured bovine pulmonary artery endothelial cell (BPAEC) albumin permeability and release of the stable metabolites of prostacyclin (i.e., 6-ketoprostaglandin [PGIFla) and thromboxane (TX)A, (i.e., TXB,).…”