Effect of endothelin on sodium/hydrogen exchanger activity of human monocytes and atherosclerosis-related functions.

The objective of this article is to investigate the influence of endothelin-1 (ET-1) on human monocyte Na(+)/H(+) exchanger (NHE) activity and on the atherosclerosis-related monocyte functions. ET-1 caused an increase in pHi and in (22)Na influx of monocytes. A reversal of ET-1 effect on pHi was observed in the presence of the NHE1 inhibitor, cariporide. In addition, the activation of NHE1 by ET-1 was mediated via protein kinase C (PKC), mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase (PI3K), and NADPH oxidase. Also, a link between ET-1 and nitric oxide (NO) was observed. Furthermore, after ET-1 treatment, an increase of the adhesive capacity, the migration ability on laminin and CD36 expression of monocytes, was observed; using cariporide this increase was abolished. Our results showed that ET-1 induces a signaling pathway with the involvement of PKC, MAPK, PI3K, and NADPH oxidase where NHE1 plays a key role. ET-1 also plays a significant role in atherosclerosis-related functions of human monocytes, via NHE1 activation.