Differential effects of intra- and extraluminal endothelin on cerebral arterioles

The differential effects of intraluminal and extraluminal application of endothelin, the endothelium-derived constricting factor, were studied in isolated intracerebral arterioles that were cannulated and perfused in vitro. Extraluminal and intraluminal application of 10(-8) M endothelin constricted the arterioles to 38.2 +/- 6.7 and 75.1 +/- 5.7% of the control diameter, respectively. Constrictions induced by either the intraluminal or the extraluminal application of endothelin were inhibited in a Ca(2+)-free solution. Nimodipine attenuated, but did not completely abolish, the constriction induced by the extraluminal application of endothelin, but it did abolish the constriction induced by the intraluminal application. The duration of vasoconstriction also differed between intra- and extraluminal application. Vessel diameter quickly returned to the control value as soon as intraluminal perfusion of endothelin was terminated. In contrast, the constriction induced by extraluminal application of endothelin lasted much longer and was difficult to reverse. The differential effect of intraluminal and extraluminal endothelin application appears to reflect the important barrier-function of the cerebrovascular endothelium of intracerebral arterioles.