Endothelium dependence of a portion of the response to cGMP in brain microcirculation of mice

The diameters of arterioles 30-40 microns on the surface of the mouse brain were monitored by TV microscopy with an image splitting technique. Endothelium was injured by light from a helium neon laser in the presence of intravascular Evans blue. This method was previously shown to selectively eliminate dilation by known endothelium dependent dilators which cause endothelial cells to release one or more relaxing factors (EDRFs). Dilation was produced by local application of 8 Br cGMP and dibutyryl cAMP, 10(-5) M. The response before endothelial damage was compared with the response after damage. Two separate studies were conducted. In one, 10 mice were treated with 8 Br cGMP and 10 with dibutyryl cAMP. In the second study 12 mice were treated with each nucleotide before endothelial injury and again after injury. In both studies only the response to 8 Br cGMP was impaired (p less than .01) by the endothelial injury. These data suggest that in these arterioles a portion of the response to GMP, but not to AMP, is controlled by endothelium and may reflect a role for guanylate cyclase/GMP in the synthesis/-release of an EDRF. This would provide a function for the guanylate cyclase in endothelial cells. The function of guanylate cyclase within these cells has not previously been defined.