Tone regulates opposing endothelium-dependent and -independent forces: resistance brain vessels in vivo

Pial arterioles on the surface of the mouse brain were observed with television microscopy and measured with an image-splitting technique. Previous studies showed that, in this vascular bed, serotonin (5-HT) and high-dose histamine produced endothelium-dependent constriction that masked and overwhelmed an endothelium-independent relaxation produced by the same agonists. Low-dose histamine produced relaxation. In the present studies we compared the responses to these agonists before and after alterations in tone. Preconstriction with uridine 5'-triphosphate caused reversal of the responses to 5-HT or high-dose histamine. These agonists now relaxed the arterioles to diameters greater than their original base line. Prerelaxation by nitroprusside caused reversal of the response to low-dose histamine. The agonist now constricted the arterioles to diameters smaller than their original base line. The data show, in vivo, in resistance vessels, that initial tone is an important determinant of the final effect or relative strengths of competing, opposing, endothelium-dependent and -independent forces triggered by a single agonist.