Endothelin-1: demonstration of potent effects on the microcirculation of humans and other species.

The effect of endothelin-1 (ET-1) on microvessels was investigated by use of intravital microscopy and by measuring microvascular blood flow changes. ET-1 caused a selective constriction of arterioles in the hamster cheek pouch, without affecting venules. A decrease in blood flow was observed at the site of intradermal injection of ET-1 in rabbit and human skin. ET-1, as a consequence of its vasoconstrictor activity, acted in an anti-inflammatory manner to inhibit edema formation and neutrophil accumulation induced by chemotactic agents in rabbit skin. In human skin, a flare, due to increased blood flow, spread for several centimeters around a central constricted area. The flare, the result of an axon reflex, reveals an alternative mechanism through which ET-1 can act to modulate vascular tone.