Prostaglandin synthesis by cells comprising the calf pulmonary artery

Abstract

Prostaglandin (PG) production was evaluated in the three cell types (endothelial, smooth muscle, and fibroblast) comprising the bovine pulmonary artery. Prostacyclin (PGI2) was the predominant prostaglandin (PG) produced by endothelial, smooth muscle, and fibroblast cells as they exist in culture or in freshly excised tissue fragments. In addition to PGI2, measurable amounts of PGE2, PGF2a, and thromboxane A2 (TXA2) were also produced by these cells. Endothelial cells were the most active producers of PGs. However, the type of PG produced was characteristic of the particular cell type, while the level of production was dependent on external factors. Prostaglandin production by cultured cells, both under basal conditions and in response to stimulatory agents, was quite similar to that of the respective freshly excised tissue fragments containing a given cell type. These cells in culture could be stimulated to produce PGI2 by both angiotensin and bradykinin at very low (physiological) concentrations, a further indication of the retention of the physiological responsiveness of these cells in culture. Endothelial cells and fibroblasts were activated by bradykinin at concentrations as low as 10(-12) M but did not respond to angiotensin. Smooth muscle cells in primary and first passage cultures were activated by both bradykinin and angiotensin at 10(-12) M concentrations. Serial subcultivations of smooth muscle cells resulted in a progressive loss in their responsiveness to bradykinin stimulation. The state of cell growth proved to be an important determinant of PG production. Actively growing cells in culture synthesized less PG when compared to cells which had entered into a "quiescent" nongrowth state.

Pharmacology of smooth muscle cell replication.

“…PGE2, PGF^, and PGI 2 are synthesized by porcine aortic smooth muscle cells supplied with exogenous arachidonic acid, but there is no secretion of thromboxane A 2 . 102 Using bovine pulmonary arterial smooth muscle cells, Menconi and colleagues 103 detected synthesis of PGF^ and PGI 2 , which was augmented by exogenous arachidonic acid. There was no detectable synthesis of PGE2 or thromboxane A 2 .…”

“…106 Thromboxane A 2 was also synthesized by excised thoracic aorta, but it is not possible to attribute this exclusively to smooth muscle cells, because endothelial cells and fibroblasts can also synthesize thromboxane A 2 . 103 Canine and human coronary arteries synthesize leukotriene (LT) C4, LTD 4 , and LTE4 when incubated in vivo with arachidonic acid and the calcium ionophore A23187. 107 Cultured rabbit aortic smooth muscle cells have been shown to generate lipoxygenase products from exogenous arachidonic acid.…”

“…Vasopressin increases PGI 2 production by the A10 smooth muscle cell line, an effect augmented by epidermal growth factor. 113 Other vasoactive agents that augment PGI 2 production include bradykinin, 114 angiotensins I and II but not angiotensin III, 103 and serotonin. 114 The ability of prostanoids to modulate the proliferation of arterial smooth muscle cells in vitro was first demonstrated by Huttner et al 100 The growth of guinea pig aortic smooth muscle cells was dose-dependently inhibited by PGE, and PGF^, the minimum effective concentrations being 2 and 20 fiM, respectively.…”

Eicosanoids in regulation of arterial smooth muscle cell phenotype, proliferative capacity, and cholesterol metabolism.

“…230 -232 - 238 These agents may, therefore, indirectly modulate smooth muscle proliferative capacity and regulation of the cholesteryl ester cycle via endothelial cell-derived eicosanoids. In addition, serotonin, 239 bradykinin, 240 and angiotensin 11240,241 m a y gigg directly stimulate smooth muscle cell eicosanoid generation. These agents have not been thought to be involved in processes controlling arterial cholesterol metabolism.…”

Interactions of bradykinin, calcium, G-protein and protein kinase in the activation of phospholipase A2 in bovine pulmonary artery endothelial cells

“…Bradykinin interaction with major blood vessels results in prostacyclin synthesis, particularly in endothelial cells [21]. In addition to its action in the vasculature, BK interacts with a variety of tissues and cell types, resulting in diverse biological activities.…”