The effects of endothelin on vascular tonus

Abstract

Using front-surface fluorometry and fura-2, the effect of endothelin (ET) on the cytosolic Ca concentration, (Ca)i, in smooth muscle cells and endothelial cells was determined. Both the contraction of smooth muscle cells and the release of endothelium-derived relaxing factor (EDRF) from endothelial cells are regulated by changes in (Ca)i. During contractions induced by U-46619, a thromboxane A2 analog, low doses of ET-1 induced an EDRF-dependent reduction of (Ca)i and force in porcine coronary arterial smooth muscles. Using porcine aortic valvular strips, we recorded the signals of (Ca)i in endothelial cells in situ. ET-1 induced an influx of Ca, which was markedly inhibited by pertussis toxin (IAP), thus indicating that this influx was regulated by an IAP-sensitive G-protein. BQ-123, a selective ETA receptor antagonist, partially inhibited the elevation of (Ca)i induced by ET-1, but did not affect the elevation of (Ca)i induced by ET-3. The sequence of cDNA encoding the porcine ETA receptor has been previously determined, and RT-PCR confirmed that ETA receptor mRNA was present in the endothelial cells on the aortic side of the valvular strips. Therefore, in addition to ETB receptors, functioning ETA receptors and ETA receptor mRNA can also be found in endothelial cells in situ. Thus, ET-1 may play an important role in controlling the coronary artery tonus not only by acting directly on smooth muscle cells to increase the force in a paracrine manner, but also by acting on endothelial cells to release EDRF in an autocrine manner, resulting in relaxation of smooth muscle cells.