Cooperation of Adipocytes and Endothelial Cells Required for Catecholamine Stimulation of PGI₂ Production by Rat Adipose Tissue

Disturbances of prostaglandin I₂ (PGI₂, prostacyclin) production by adipose tissue contribute to the pathogenesis of diabetic ketoacidosis and may contribute to the pathogenesis of hypertension and vascular disease. We studied the cellular basis of PGI₂ production in adipose tissue, measured as release of 6-keto-PGF_1α in response to epinephrine. Adipocytes did not produce PGI₂ when nonfat cells were removed by repeated washing. The nonadipocyte cellular constituents of adipose tissue (nonfat cells) did not produce PGI2 in the absence of adipocytes. Both adipocytes and nonfat cells were required for PGI₂ production in response to epinephrine. Adipocytes pretreated with 0.2 mM aspirin to inhibit PGH synthase nevertheless promoted PGI₂ production when mixed with nonfat cells. Nonfat cells preincubated with aspirin did not produce PGI₂ when mixed with adipocytes. The nonfat cells converted arachidonic acid to PGI₂ but adipocytes did not. Epinephrine stimulated lipolysis and PGI₂ production in a dose-dependent parallel manner, but the responses were distinct above 10⁻⁶ M. Characterization of the nonfat cells by fractionation on a Percoli density gradient followed by measurement of angiotensincon vert ing enzyme activity and 6-keto-PGF_1α production indicated that the nonfat cells were predominantly vascular endothelial cells. We conclude that catecholamine-stimulated PGI₂ production in adipose tissue results from the cooperation of adipocytes and vascular endothelial cells. The adipocytes provide arachidonic acid, which is converted to PGI₂ by the vascular endothelial cells. Because adipose tissue is located near blood vessels throughout the body, adipocytes may be an important source of arachidonic acid for vascular endothelial cells in various circumstances in health and disease. Our findings raise the possibility that adipocytes may, under some circumstances, release arachidonic acid into the systemic circulation where it is used by vascular endothelial cells throughout the body to produce PGI₂ and other eicosanoids.