Hepatic parenchymal cell metabolic status does not control the hepatic arterial blood flow. Portal blood flow is a major intrinsic regulator of hepatic arterial tone. Hepatic arterial blood flow changes so as to buffer the impact of portal flow alterations on total hepatic blood flow, thus tending to regulate total hepatic flow at a constant level. This response is called the "hepatic arterial buffer response." The mechanism of the arterial buffer response seems to depend on portal blood flow washing away local concentrations of adenosine (production may be constant) from the area of the arterial resistance site. If portal flow decreases, less adenosine is washed away and the local concentration rises resulting in arterial dilation. Putative roles. Hepatic clearance of many hormones and endogenous compounds is blood flow limited. Constancy of total hepatic blood flow is crucial to homeostasis, and severe changes in the magnitude of flow can rapidly alter plasma concentrations of such compounds. The buffer may also prevent portal flow changes from severely altering intrahepatic blood pressures and liver blood volume. Pathological implications. If the O2 supply-to-demand ratio becomes too low, as in the case of a hypermetabolic liver (chronic alcohol exposure), a state of tissue hypoxia can exist without producing hepatic arterial dilation. Therapeutic implications. Livers show protection and improved recovery from several toxic agents, including alcohol, if the O2 supply-to-demand ratio can be increased. Arterial dilation by means of intra-arterial or intra-portal adenosine may prove useful.