Loss of endothelium-dependent relaxation in mouse cerebral microvessels may be rapidly reversible

This study demonstrates that a loss of endothelium-dependent relaxation in brain microvessels can be rapidly reversible. This loss was produced by injuring the endothelium in situ with a HeNe laser in the presence of intravascular Evans blue. The noxious stimulus has previously been shown not to damage vascular smooth muscle. The loss of endothelium-dependent relaxation was manifest by loss of dilating responses to both acetylcholine (ACh) and bradykinin (BK). Both agents have been shown by others to produce an endothelium-dependent relaxation in large vessels, caused by endothelial release of one or more endothelium-dependent relaxing factor(s) or EDRF(s). Previous studies have not tested for rapid return of endothelium-dependent relaxation after initial loss. In large vessels this might not be expected if reports concerning the necessary removal of large amounts of endothelium are correct. In cerebral microvessels, however, we have already shown apparent loss of EDRF following only minimal ultrastructural alteration of intact endothelial cells. The question remained whether these morphologic alterations reflected the onset of irreversible changes. The present study suggests that these cells were not irreversibly damaged, at least with respect to apparent modulation of endothelium-dependent responses. Recovery of responses to both ACh and BK occurred within 1 hr of initial injury and initial loss of endothelium-dependent relaxation. Recovery within 1 hr did not occur at the center of laser injury, but at a site of impaired response 55 micron away. Previous studies had suggested less dramatic injury of endothelium here compared with endothelium at the center of laser impact.(ABSTRACT TRUNCATED AT 250 WORDS)