Altering hydrodynamic variables influences PGI2 production by isolated lungs and endothelial cells.
Because deformation of lung tissue stimulates prostaglandin synthesis, we wanted to investigate whether hydrodynamic forces would affect lung prostacyclin (PGI2) production. To test the hypothesis that lung prostacyclin synthesis was flow dependent, we examined lung prostacyclin production after flow alterations. Using a salt solution that contained either Ficoll or albumin as a perfusate, we changed the flow to half and to double the control flow. When flow was changed, lung prostacyclin production followed changes in flow and pressure drop. When flow was varied in lungs treated with indomethacin, prostacyclin production was too low to be measurable. Variations in pressure pulsatility at constant mean flow had no influence on lung prostacyclin production. Since vascular distension may also stimulate prostacyclin production, we increased venous pressure. An increase in venous pressure (from 2.1 to 4.8 mmHg) had no effect on prostacyclin production; a further increase in venous pressure (to 7.5 mmHg) initiated edema and caused a large increase in prostacyclin production. When we subjected monolayers of endothelial cells cultured in wells to defined shear rates, the prostacyclin concentration in the supernatant quickly increased to a maximum. The absence of further increase with greater shear may have reflected feedback control of prostacyclin synthesis. The results indicated that hydrodynamic disturbances affect endothelial cells and stimulate arachidonate metabolism. Lung prostacyclin production may be related to flow. However, this effect is small compared with the lung prostacyclin production during edema formation.
D000818:Animals; D004727:Endothelium / Q000166:cytology / Q000378:metabolism; D011464:Epoprostenol / Q000096:biosynthesis*; D006439:Hemodynamics; D066298:In Vitro Techniques; D008168:Lung / Q000378:metabolism*; D008297:Male; D010827:Physiology / Q000295:instrumentation; D011453:Prostaglandins / Q000096:biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains; D014690:Venous Pressure
D011453:Prostaglandins; D011464:Epoprostenol