ENDOTHELIAL STIMULATION OF SODIUM-PUMP IN CULTURED VASCULAR SMOOTH-MUSCLE

We studied vascular sodium pump activity and its regulation by vasoact ive agents and endothelium in cultured aortic vascular smooth muscle c ells from normotensive Wistar-Kyoto rats (WKY) and spontaneously hyper tensive rats (SHR). Baseline sodium pump activity (ouabain-inhibitable Rb-86(+) uptake) was similar in cells from both rat strains. Angioten sin II and endothelin-1 increased ouabain-inhibitable Rb-S6(+) uptake more in SHR than WKY cells, whereas no effects were obtained with sodi um nitroprusside, 8-bromo-cGMP, or iloprost. We examined the influence of endothelium on vascular sodium pump activity either by coculturing smooth muscle and endothelial cells or by using conditioned medium. B oth coculture for 24 hours with endothelial cells and treatment with c onditioned medium increased smooth muscle cell sodium pump activity, t his effect being higher in SHR cells. These results suggest that the e ndothelium may modulate sodium pump activity in the underlying smooth muscle by releasing a diffusible compound, which is more active on SHR smooth muscle. The conditioned medium obtained in the presence of inh ibitors of angiotensin-converting enzyme, endothelin-1-converting enzy me, cyclooxygenase, lipoxygenase, and nitric oxide synthase had no eff ect on the ability of conditioned medium to increase sodium pump activ ity, suggesting that angiotensin II, endothelin-1, eicosanoids, and ni tric oxide are not involved in this stimulatory effect. The nature of the possible endothelial factor involved is still unknown, but it poss esses a molecular weight between 25 and 50 kD, is heat stable,and is s ensitive to trypsin treatment. We propose it could be a growth factor.