Vascular effects of platelet-activating factor in lambs: role of cyclo- and lipoxygenase

Abstract

In adult sheep, platelet-activating factor (PAF) effects include systemic hypotension and pulmonary hypertension. To identify developmental differences in vascular responses to PAF, we studied the effects of C18- and C16-PAF in 49 +/- 2- (SE) day-old lambs. Responses of upstream (arteries and microvessels) and venous segments of the lung to C18-PAF were determined both in vivo and in isolated lungs. In isolated lungs, the role of eicosanoids in PAF effects was also determined. In vivo, both C18- and C16-PAF caused a significant increase in systemic and pulmonary vascular resistance. The magnitude of vascular responses to C16-PAF was greater than that to C18-PAF. C18-PAF constricted both upstream and venous segments of the pulmonary circulation. Cyclooxygenase inhibition in isolated lungs attenuated arterial constriction to C18-PAF, whereas simultaneous cyclooxygenase and lipoxygenase inhibition completely blocked the effects of C18-PAF. In summary, in contrast to PAF effects in adult sheep, PAF constricts both systemic and pulmonary vessels in lambs, with significant pulmonary venous constriction. Eicosanoids, especially lipoxygenase products, play a major role in mediating PAF effects in the lung.

Platelet-Activating Factor Modulates Activity of Cyclic Nucleotides in Fetal Ovine Pulmonary Vascular Smooth Muscle

“…In fetal pulmonary circulation, vasoconstrictors such as PAF and thromboxane A 2 (Toga et al, 1992;Argiolas et al, 1995;Ibe et al, 1998) maintain high vasomotor tone by increasing intracellular levels of IP 3 and calcium. At birth, release of vasodilators such as cGMP and cAMP induce smooth muscle relaxation by acting through their respective protein kinases, PKG and PKA (Dhanakoti et al, 2000;Abdel-Latif, 2001).…”

“…All studies were done with smooth muscle cells harvested from intrapulmonary veins of term fetal lambs, because they exhibit more PAF binding than cells from arteries (Ibe et al, 2005). Also, we have previously reported that in the fetus, pulmonary veins often demonstrate significantly greater vasoactivity than pulmonary arteries, and veins contribute a significant fraction to pulmonary vascular resistance in utero (Kääpä et al, 1991;Toga et al, 1992).…”

“…In lungs, PAF is a potent vasoactive mediator with different sites of action in different species (Toga et al, 1992;Argiola et al, 1995;Ibe et al, 1998). In the fetus, PAF plays an important physiological role in maintaining a high vasomotor tone in the pulmonary circulation (Ibe et al, 1998).…”

The inositol trisphosphate pathway mediates platelet-activating-factor-induced pulmonary oedema

“…In vivo, besides bronchoconstriction [22], PAF produces many effects that may contribute to oedema formation, for example, hydrostatic mechanisms, such as activation of neutrophils [23,24], pulmonary vasoconstriction [25,26] and platelet aggregation [24]. Although these factors may aggravate pulmonary oedema, the major factor in PAF-induced oedema formation appears to be increased vascular permeability.…”

Analysis of a nucleotide-binding site of 5-lipoxygenase by affinity labelling: binding characteristics and amino acid sequences

“…They have been implicated as mediators in asthma and other types of allergic reaction [1]. Recent reports have also shown that 5LO is involved in tumour cell proliferation [2][3][4][5][6][7] and is related to primary pulmonary hypertension [8][9][10][11][12].…”